The interplay between the gut microbiota and gastrointestinal hormones plays a pivotal role in the health of the host and the development of diseases. As a vital component of the intestinal microecosystem, the gut microbiota influences the synthesis and release of many gastrointestinal hormones through mechanisms such as modulating the intestinal environment, producing metabolites, impacting mucosal barriers, generating immune and inflammatory responses, and releasing neurotransmitters. Conversely, gastrointestinal hormones exert feedback regulation on the gut microbiota by modulating the intestinal environment, nutrient absorption and utilization, and the bacterial biological behavior and composition. The distributions of the gut microbiota and gastrointestinal hormones are anatomically intertwined, and close interactions between the gut microbiota and gastrointestinal hormones are crucial for maintaining gastrointestinal homeostasis. Interventions leveraging the interplay between the gut microbiota and gastrointestinal hormones have been employed in the clinical management of metabolic diseases and inflammatory bowel diseases, such as bariatric surgery and fecal microbiota transplantation, offering promising targets for the treatment of dysbiosis-related diseases.

What can be regarded as a seedling of the contemporary aquaculture in the Mediterranean began back in the 1950s. The development of the industry did not always align with the development of ichthyopathology, a veterinary discipline aimed at identifying and combating fish diseases. Therefore, and due to the lack of published data, we are not always able to pinpoint the first outbreaks that accompanied the increase in aquaculture production. Nonetheless, fish pathogens, and parasites in particular, have shown diversity related to host species, their farming conditions and geography. Two parasite species currently regarded as dominant in Mediterranean aquaculture are the histozoic myxozoan Enteromyxum leei and the haematophagous polyopisthocotylean Sparicotyle chrysophrii, both of which infect gilthead seabream (Sparus aurata). The interactions between parasite and host with regard to the immune activity of both have been well studied using conventional immunology and omics approaches. For the remaining parasite-fish systems, our understanding of host responses and parasite mitigation mechanisms is still vague and mostly transposed from what we know of other systems. This review compiles the knowledge on fish response to the most frequent and economically important parasites in Mediterranean aquaculture, highlights the gaps and suggests further directions.

Immunotherapy is an emerging strategy that awakens the intrinsic immune system for cancer treatment. Generally, successful immunotherapy of malignant tumours relies on the effective production of tumour-associated antigens and their lymph node delivery, antigen processing and presentation for T-cell activation, and the dismantling of the immunosuppressive tumour microenvironment. Toll-like receptor (TLR) agonists are potent stimulants in cancer immunotherapy, which can directly activate antigen-presenting cells (APCs) and further induce T cell activation for antitumour immune response and convert immunosuppressive tumour microenvironment to an immunogenic one for cooperative tumour ablation. However, TLR agonists for effective cancer immunotherapy have encountered essential challenges, such as insufficient immune activation and systemic side effects. In recent years, nano-immunomodulators with TLR agonists have been employed for tumour- and/or lymph node-targeted immune activation to improve the antitumour immune response and alleviate their systemic toxicities, providing a promising strategy for enhanced cancer immunotherapy. Herein, we introduce the recent progress in developing various TLR nano-immunomodulators for cancer immunotherapy via APC activation and tumour microenvironment remodelling. Upon elucidating the rational design principles of nano-immunomodulators, we elucidate the advancement of TLR nanoagonists to break the barriers in effective and safe Toll-like receptor stimulation for potent cancer immunotherapy.

Scavenger receptors (SRs) are crucial for pattern recognition in the innate immune system. However, the role of Scavenger Receptors class A member 5 (SRA5) in the immunological response of bony fish to pathogen invasion remains unclear. This study identified and characterized the SRA5 of Lateolabrax maculatus (LmSRA5) from its transcriptome database. LmSRA5 has a 1494 bp open reading frame, encodes 497 amino acids, has a molecular weight of 55.01 kDa, and contains a collagen domain and a conserved Scavenger Receptor Cysteine-Rich domain. LmSRA5 exhibited high sequence similarity to previously reported SRA5 genes. LmSRA5 exhibited high sequence similarity to previously reported SRA5 genes. LmSRA5 is primarily localized in the cytoplasm, with its encoded proteins distributed in both the cytoplasm and the cell membrane. LmSRA5 was expressed in all tissues. The highest expression was observed in the pituitary gland, with significant levels in the stomach, intestines, liver, and kidney. LmSRA5 expression in the head kidney, spleen, blood, and intestines initially increased, then decreased following infection with Aeromonas veronii. The binding affinity of LmSRA5 for A. veronii was enhanced by increasing concentrations of the extracellular domain recombinant LmSRA5. Knockdown and overexpression experiments in liver cells demonstrated that LmSRA5 significantly regulates the expression of IL-8 and c-Jun. LmSRA5 participates in the immune response by recognizing pathogen-associated molecular patterns (PAMPs) and contributes to immune regulation through modulation IL-8 and c-Jun. This study offers valuable insights into the role of SRA5 in pathogen resistance and immune regulation in bony fish, thereby contributing to the advancement of aquaculture under escalating disease pressures.

In recent years, the marked augment of antibiotic resistance hampered the development of antibacterial agent. Nanozymes by their in situ ROS production capability oxidize cellular substances of bacterial cell and eliminate MDR bacteria. Therefore, synthesis of effective nanozymes from green precursors is rarely reported, so the prime objective of this study was to synthesize Cu-Mn3O4 nanozymes from aqueous extracts of medicinal plant Azadirachta indica via co-precipitation approach and to endorse their biomedical applications. The synthesized materials were characterized by X-ray diffraction (XRD), Fourier Transform Infrared spectrometer (FTIR), Scanning Electron Images (SEM), and Field-Emission Scanning Electron Microscopy (FESEM) images. X-ray Diffraction (XRD) patterns revealed the formation of hausmannite Mn3O4 crystal system. Fourier Transform Infrared spectrometer (FTIR) spectra revealed functional groups on the surface nanoparticles for their stabilization. Energy-Dispersive X-ray spectroscopy (EDAX) profile confirmed the existence of desired elements in the synthesized nanozymes. B1 mimics oxidase enzyme most effectively with Km = 0.175 mM and Vmax = 10.34 µM/min. The low Km and high Vmax indicates the strong binding affinity and high catalytic activity. From the agar diffusion antibacterial assay, it can be concluded that B3 is the most potent antibacterial agent specifically against Gram-positive bacteria Bacillus subtilis with inhibition zone of 27 mm at 250 µg/mL. Their cytotoxic activities on neuroblastoma (SHSY5) cell line were investigated for the first time. The data revealed that synthesized nanooctahedrons possess a significant cytotoxicity against cancer cell lines SHSY5Y (IC50 = 137.47 ± 14.11 µg/mL) and SKOV3 (IC50 = 72.72 ± 9.33 µg/mL). Overall, with increasing Cu amount, the percentage growth inhibition of Mn3O4 crystal system enhanced. The improved antibacterial activity and cytotoxicity is due to synergy between metal and phytochemicals. Radical scavenging activity of synthesized nanozymes is comparatively lower than their green source and the comparatively lower IC50 values of B1, 234.12 ± 15.13 and 220.12 ± 10.37 respectively, which indicates that it is more active in scavenging DPPH and ABTS radical. B2 (IC50 = 310.56 ± 5.92 µg/mL) and B3 (IC50 = 43.56 ± 3.03 µg/mL) scavenge superoxide radicals and FRAP more effectively. It is noticed that synthesized nanozymes have greater antibacterial and anticancer activity but low scavenging ability compared to green extract. Thus, Cu-Mn3O4 NPs from Azadirachta indica leaf extract could be utilized as a replacement of potential antibiotic drug candidate against MDR bacteria and in cancer avenues.

In 2020, sepsis has been defined a worldwide health major issue (World Health Organization). Lung, urinary tract and abdominal cavity are the preferred sites of sepsis-linked infection. Research has highlighted that the advancement of sepsis is not only related to the presence of inflammation or microbial or host pattern recognition. Clinicians and researchers now recognized that a severe immunosuppression is also a common feature found in patients with sepsis, increasing the susceptibility to secondary infections. Lipopolysaccharides (LPS) are expressed on the cell surface of Gram-negative, whereas Gram-positive bacteria express peptidoglycan (PGN) and lipoteichoic acid (LTA). The main mechanism by which LPS trigger host innate immune responses is binding to TLR4-MD2 (toll-like receptor4-myeloid differentiation factor 2), whereas, PGN and LTA are exogenous ligands of TLR2. Nucleotide-binding oligomerization domain (NOD)-like receptors are the most well-characterized cytosolic pattern recognition receptors, which bind microbial molecules, endogenous by-products and environmental triggers. It has been demonstrated that high-density lipoproteins (HDL), besides their major role in promoting cholesterol efflux, possess diverse pleiotropic properties, ranging from a modulation of the immune system to anti-inflammatory, anti-apoptotic, and anti-oxidant functions. In addition, HDL are able at i) binding LPS, preventing the activating of TLR4, and ii) inducing the expression of ATF3 (Activating transcription factor 3), a negative regulator of the TLR signalling pathways, contributing at justifying their capacity to hamper infection-based illnesses. Therefore, reconstituted HDL (rHDL), constituted by apolipoprotein A-I/apolipoprotein A-IMilano complexed with phospholipids, may be considered as a new therapeutic tool for the management of sepsis.

Light-field microscopy (LFM) and its variants have significantly advanced intravital high-speed 3D imaging. However, their practical applications remain limited due to trade-offs among processing speed, fidelity, and generalization in existing reconstruction methods. Here we propose a physics-driven self-supervised reconstruction network (SeReNet) for unscanned LFM and scanning LFM (sLFM) to achieve near-diffraction-limited resolution at millisecond-level processing speed. SeReNet leverages 4D information priors to not only achieve better generalization than existing deep-learning methods, especially under challenging conditions such as strong noise, optical aberration, and sample motion, but also improve processing speed by 700 times over iterative tomography. Axial performance can be further enhanced via fine-tuning as an optional add-on with compromised generalization. We demonstrate these advantages by imaging living cells, zebrafish embryos and larvae, Caenorhabditis elegans, and mice. Equipped with SeReNet, sLFM now enables continuous day-long high-speed 3D subcellular imaging with over 300,000 volumes of large-scale intercellular dynamics, such as immune responses and neural activities, leading to widespread practical biological applications.

Osteoimmunomodulation is a strategy to promote bone regeneration in implants by modifying the immune environment. CpG-containing oligonucleotides type C (CpG ODN C) and Polyinosinic:polycytidylic acid (Poly[I:C]) are analogs of microbial nucleic acids that have been studied for various immunotherapeutic applications. This research investigates the potential of CpG ODN C and Poly(I:C) as an osteoimmunomodulatory agent for bone regenerative purposes. We encapsulated each nucleic acid in a lipid-based nanoparticle to facilitate the delivery into intracellular pathogen recognition receptors in immune cells. The lipid-based nanoparticles were ±250 nm in size with a negative charge (-36 to -40 mV) and an encapsulation efficiency of ±60 %. Lipid-based nanoparticles containing nucleic acids, Lip/CpG ODN C and Lip/Poly(I:C), increased the production of TNF, IL-6, and IL-10 by primary human macrophages compared to free-form nucleic acids. Conditioned medium from macrophages treated with CpG ODN C (10 µg/ml) and Lip/CpG ODN C (0.1, 1, and 10 µg/ml) promoted osteoblast differentiation of human mesenchymal stromal cells by 2.6-fold and 3-fold, respectively; no effect was seen for Lip/Poly(I:C). Bone implants were prepared, consisting of a biphasic calcium phosphate scaffold, bone morphogenetic protein (BMP) 2, and lipid-based nanoparticles suspended in gelatin methacryloyl (GelMA) hydrogel. Implants were evaluated for de novo bone formation in an extra-skeletal implantation model in rabbits for 5 weeks. Based on the particles suspended in GelMA, six groups of implants were prepared: Lip/CpG ODN C, Lip/Poly(I:C), Lip (empty), CpG ODN C, Poly(I:C), and a control group consisting of empty GelMA. After 5 weeks, healthy bone tissue formed in all of the implants with active osteoblast and osteoclast activity, however, the amount of new bone volume and scaffold degradation were similar for all implants. We suggest that the working concentrations of the nucleic acids employed were inadequate to induce a relevant inflammatory response. Additionally, the dosage of BMP-2 used may potentially mask the immune-stimulatory effect. Lip/CpG ODN C holds potential as a bioactive agent for osteoimmunomodulation, although further in vivo demonstration should corroborate the current in vitro findings.

Evidence indicates that Poria cocos polysaccharide (PCP) improves cognitive impairment in Alzheimer's disease (AD); however, its underlying mechanism, particularly its relationship with the gut microbiota, remains unclear. In the current study, we aimed to investigate the mechanism of PCP in improving cognitive impairment in AD. The results demonstrated that PCP markedly enhanced cognitive function and mitigated AD-related pathological alterations in 3 × Tg-AD mice. PCP treatment reversed the age-dependent gut microbiota dysbiosis in 3 × Tg-AD mice by 16S rDNA sequencing. The contents of propanoic acid, butanoic acid and isohexanoic acid were increased by short-chain fatty acid determination. In addition, PCP could restore both the intestinal barrier and the blood-brain barrier, as demonstrated by immunofluorescence staining of tight junction proteins. Furthermore, PCP alleviated systemic inflammation and neuroinflammation, as evidenced by reduced LPS levels in circulation and decreased IL-6 levels in the brain, likely by inhibiting the TLR4/NF-κB signaling pathway. In conclusion, PCP can reshape gut microbiota to regulate short-chain fatty acids and alleviate neuroinflammation-related cognitive impairment in AD mice.

The human body functions as a complex ecosystem, hosting trillions of microbes that collectively form the microbiome, pivotal in immune system regulation. The host-microbe immunological axis maintains homeostasis and influences key physiological processes, including metabolism, epithelial integrity, and neural function. Recent advancements in microbiome-based therapeutics, including probiotics, prebiotics and fecal microbiota transplantation, offer promising strategies for immune modulation. Microbial therapies leveraging microbial metabolites and engineered bacterial consortia are emerging as novel therapeutic strategies. However, significant challenges remain, including individual microbiome variability, the complexity of host-microbe interactions, and the need for precise mechanistic insights. This review comprehensively examines the host microbiota immunological interactions, elucidating its mechanisms, therapeutic potential, and the future directions of microbiome-based immunomodulation in human health. It will also critically evaluate challenges, limitations, and future directions for microbiome-based precision medicine.

Minimally invasive irreversible electroporation ablation shows promise for pancreatic cancer (PCa), but the high recurrence and metastasis rates pose a therapeutic challenge for loco-regional ablation treatment. Immunotherapy holds promise for preventing tumor recurrence, however, its efficacy against PCa remains limited. Here, using a preclinical model of PCa, it is identified that tumor development dramatically restructures the splenic immune landscape characterized by increased frequency of myeloid cells. Further, nanobiologics with high affinity for splenic myeloid cells using erythrocyte membrane fused with apoA1-modified liposomes are presented. Biocompatible CaCO3 nanoparticles are incorporated to serve as a release reservoir of immunomodulatory therapeutics (muramyl dipeptide, MDP). The nanobiologics, MDCa@RBC-Alipo, induce antitumor-trained immunity by epigenetically and metabolically rewiring splenic myeloid cells, thereby overcoming the immunosuppressive tumor microenvironment in residual PCa following irreversible electroporation ablation. This approach enhances the therapeutic efficacy of aPD-L1 and significantly inhibits tumor recurrence and hemorrhagic ascites development. The trafficking of MDP directly to the spleen highlights a previously uncharacterized pathway for inducing peripheral trained immunity, thereby presenting a novel therapeutic approach for locally advanced PCa treatment.

Cytokines interact with their receptor complexes to orchestrate diverse processes-from immune responses to behavioral modulation. Interleukin-17A (IL-17A) mediates protective immune responses by binding to IL-17 receptor A (IL-17RA) and IL-17RC subunits. IL-17A also modulates social interaction, yet the role of cytokine receptors in this process and their expression in the brain remains poorly characterized. Here, we mapped the brain-region-specific expression of all major IL-17R subunits and found that in addition to IL-17RA, IL-17RB-but not IL-17RC-plays a role in social behaviors through its expression in the cortex. We further showed that IL-17E, expressed in cortical neurons, enhances social interaction by acting on IL-17RA- and IL-17RB-expressing neurons. These findings highlight an IL-17 circuit within the cortex that modulates social behaviors. Thus, characterizing spatially restricted cytokine receptor expression can be leveraged to elucidate how cytokines function as critical messengers mediating neuroimmune interactions to shape animal behaviors.

Intricate interactions between immune cells and cytokines define psoriasis, a chronic inflammatory skin condition that is immunological-mediated. Cytokines, including interleukins (ILs), interferons (IFNs), tumor necrosis factors (TNFs), chemokines, and transforming growth factor-β (TGF-β), are essential for controlling cellular activity and immunological responses, maintaining homeostasis and contributing to the pathogenesis of psoriasis. These molecules modulate the immune microenvironment by either promoting or suppressing inflammation, which significantly impacts therapeutic outcomes. Recent research indicates that treatment strategies targeting cytokines and chemokines have significant potential, offering new approaches for regulating the immune system, inhibiting the progression of psoriasis, and reducing adverse effects of traditional therapies. This review consolidates current knowledge on cytokine and chemokine signaling pathways in psoriasis and examines their significance in treatment. Specific attention is given to cytokines like IL-17, IL-23, and TNF-α, underscoring the necessity for innovative therapies to modulate these pathways and address inflammatory processes. This review emphasizes the principal part of cytokines in the -pathological process of psoriasis and explores the challenges and opportunities they present for therapeutic intervention. Furthermore, we examine recent advancements in targeted therapies, with a particular focus on monoclonal antibodies, in ongoing research and clinical trials.

Various immunotherapeutic strategies are being developed to fight cancer, which is one of the leading causes of mortality. Dendritic cells (DCs), being professional antigen-presenting cells, after efficient manipulation with tumor-associated antigens, can lead to effective T-cell recruitment and activation at the tumor site, resulting in cytotoxic T-cell-mediated cancer cell killing. To circumvent the inefficiencies of ex vivo DC modification and patient infusion, an alternative strategy involving in situ DC activation has been explored here. Here, the vaccine components are tumor lysates, as antigens, and polyinosinic:polycytidylic acid (poly(I:C)), a toll-like receptor-3 (TLR3) agonist, as an adjuvant. Our in vitro studies demonstrate that complexing poly(I:C) with a carrier molecule, chitosan, enhances its stability and accessibility to TLR3 in the DC endosomal membrane. Material-based localized delivery of immunomodulatory factors is known to improve their stability and reduce their off-target side effects. Here, PEGDA-PLL-based macroporous scaffolds allow easy recruitment of host cells, thereby enabling effective interaction between the vaccine components loaded on them and the infiltrating immune cells. The vaccine components present in the scaffold facilitate efficient DC activation and migration, leading to subsequent T-cell activation and antitumor response, as shown by our in vivo studies.

Cytotoxic killing is an essential immune function, yet its cellular mechanisms have been characterized in only a few model species. Here, we show that planarian flatworms harness a unique cytotoxic strategy. In planarians, activin, a hormone regulating regeneration and reproduction, also acts as an inflammatory cytokine. Overactivation of activin signaling - through protein injection, genetic chimerism, or bacterial infection - triggers 'ruptoblasts', an undocumented immune cell type, to undergo 'ruptosis', a unique mode of cell bursting that eliminates nearby cells and bacteria in mere minutes, representing one of the fastest cytotoxic mechanisms observed. Ablating ruptoblasts suppresses inflammation but compromises bacterial clearance, highlighting ruptoblasts' broad-spectrum immune functions. We further identified ruptoblast-like cells in diverse basal bilaterians, unveiling an alternative strategy that couples hormonal regulation with immune defense and expanding the landscape of evolutionary immune innovations.

Bacteria-based vaccines have received increasing attention given the ability to induce strong systemic immune responses. However, the application of bacteria as therapeutic agents inevitably suffers from infection-associated side effects due to the living characteristics. Here, the use of bacteria-derived flagella is described to construct self-adjuvated nanofiber vaccines. With the help of charge-reversal mediated by decoration with cationic polymers, the flagella can be coated with negatively charged antigens through electrostatic interaction. By virtue of the large aspect ratio, the resulting nanofiber vaccines show prolonged retention at the injection site and increased uptake by dendritic cells and macrophages. Thanks to the innate immunogenicity, self-adjuvated flagella robustly promote dendritic cell maturation and macrophage polarization, resulting in the elicitation of antigen-specific T-cell and B-cell immune responses. In ovalbumin-overexpressing melanoma-bearing mice, immunization with ovalbumin-carried vaccines not only exhibits a favorable tolerance, but also displays superior inhibition efficacies on tumor growth and metastasis separately under the therapeutic and prophylactic settings. The flexibility of this approach is further demonstrated for vaccine fabrication by coating with the SARS-CoV-2 Spike protein S1 subunit. Bacterial flagella-based self-adjuvated nanofiber platform proposes a versatile strategy to develop various vaccines for disease prevention and treatment.

Macrophage polarization is a dynamic process driven by a complex interplay of cytokine signaling, metabolism, and epigenetic modifications mediated by pathogens. Upon encountering specific environmental cues, monocytes differentiate into macrophages, adopting either a pro-inflammatory (M1) or anti-inflammatory (M2) phenotype, depending on the cytokines present. M1 macrophages are induced by interferon-gamma (IFN-γ) and are characterized by their reliance on glycolysis and their role in host defense. In contrast, M2 macrophages, stimulated by interleukin-4 (IL-4) and interleukin-13 (IL-13), favor oxidative phosphorylation and participate in tissue repair and anti-inflammatory responses. Metabolism is tightly linked to epigenetic regulation, because key metabolic intermediates such as acetyl-coenzyme A (CoA), α-ketoglutarate (α-KG), S-adenosylmethionine (SAM), and nicotinamide adenine dinucleotide (NAD+) serve as cofactors for chromatin-modifying enzymes, which in turn, directly influences histone acetylation, methylation, RNA/DNA methylation, and protein arginine methylation. These epigenetic modifications control gene expression by regulating chromatin accessibility, thereby modulating macrophage function and polarization. Histone acetylation generally promotes a more open chromatin structure conducive to gene activation, while histone methylation can either activate or repress gene expression depending on the specific residue and its methylation state. Crosstalk between histone modifications, such as acetylation and methylation, further fine-tunes macrophage phenotypes by regulating transcriptional networks in response to metabolic cues. While arginine methylation primarily functions in epigenetics by regulating gene expression through protein modifications, the degradation of methylated proteins releases arginine derivatives like asymmetric dimethylarginine (ADMA), which contribute directly to arginine metabolism-a key factor in macrophage polarization. This review explores the intricate relationships between metabolism and epigenetic regulation during macrophage polarization. A better understanding of this crosstalk will likely generate novel therapeutic insights for manipulating macrophage phenotypes during infections like tuberculosis and inflammatory diseases such as diabetes.

Mycoplasmas are the smallest cell-wall-less self-replicating prokaryotes. Mycoplasma species can be found within and outside cells as "silent parasites" that live intracellularly and as membrane surface parasites. The pathogen's impact on respiratory health seems primarily caused by its capacity to alter immune responses, cause airway inflammation, and damage epithelial barriers. Much progress has been made in understanding Mycoplasma-induced inflammation and oxidative stress. However, there are still issues in therapeutic management, such as the development of strains that are resistant to antibiotics, the shortcomings of the available diagnostic techniques, and possible long-term respiratory consequences. On the other hand, to combat oxidative stress, inflammation, and metabolic abnormalities, activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is becoming a more appealing therapeutic strategy. Nrf2 activation coordinates a thorough defense through its transcriptional targets, enabling adaptability and survival under a variety of cellular stressors. Nrf2 is regarded as a therapeutic target, and pharmacological Nrf2 activators have demonstrated protective effects in multiple pathological consequences and advantages in clinical trials. In this review, we discussed the rationale for targeting Nrf2 in a series of inflammatory responses caused by Mycoplasma species.

The chapter talks about how our body and mind respond to stress and how it affects our immune system. Stress reactions, especially the fight-or-flight reaction, are helpful at first but can be harmful if they last too long. Long-term stress, caused by hormones like cortisol and adrenaline, weakens the immune system and makes people more likely to get sick. Important brain chemicals like serotonin and norepinephrine help control how our immune system works. Also, the connection between our gut and brain is an important way that mental health affects how our immune system functions. Getting older and experiencing stress early in life can affect how our immune system works. Inflammation caused by stress is connected to health issues like heart disease, depression, and autoimmune diseases. There are ways to manage stress, like being mindful and having support from friends, are important for keeping your immune system healthy and lessening harm caused by stress.

The recent rise in effective immuno-oncology therapies has increased demand for experimental approaches to model anticancer immunity. A variety of mouse models have been developed and used to study cancer immunology. These include mutagen-induced, genetically engineered, syngeneic, and other models of cancer immunology. These models each have the potential to define mechanistic aspects of anticancer immune responses, identify potential therapeutic targets, and serve as preclinical models for further therapeutic development. Specific benefits and liabilities are characteristic of particular cancer immunology modeling approaches. The optimal choice and utilization of models depends on the cancer immunology scientific question being addressed and can serve to increase mechanistic understanding and development of human immuno-oncology therapies.

TLR2 is a key component of the innate immune system, responsible for recognizing Gram-positive bacterial components and initiating inflammatory signaling cascades that activate defense responses. However, little is known about the regulatory effects of Pseudomonas aeruginosa (P. aeruginosa) on TLR2 expression. In this study, we investigated the potential link between P. aeruginosa-derived DnaJ and TLR2 expression in macrophages, as well as the activation of downstream signaling pathways. Our findings revealed that DnaJ significantly induced TLR2 expression in a dose- and time-dependent manner, predominantly affecting TLR2 with minimal impact on other TLRs, such as TLR4 and TLR5, which detect bacterial PAMPs. The DnaJ-mediated TLR2 induction was driven by activation of the PI3K-SGK1 signaling pathway, with TLR10 playing a crucial role in facilitating these effects. This increase in TLR2 expression led to enhanced production of inflammatory cytokines in response to secondary Staphylococcus aureus infections, indicating a role in boosting host defense mechanisms. In conclusion, these findings suggest that P. aeruginosa-derived DnaJ promotes TLR2 expression via TLR10-mediated activation of the PI3K-SGK1 pathway, thereby enhancing host immune responses against Gram-positive bacterial infections.

The puff adder (Bitis arietans) is a medically important snake species found across much of Africa, yet there is limited literature on the clinical features and pathophysiology of envenoming after a puff adder bite.

We conducted a case-series study to describe the clinical features of patients with puff adder bites who were treated in two primary healthcare facilities in Kenya and complemented our case-series with a scoping review of all published cases of puff adder envenoming that contained sufficient clinical details to highlight the major features.

Between December 2020 and September 2021, 15 patients were admitted with a suspected puff adder bite (based on the patient's description of the biting snake or confirmed in patients who brought the dead snake or a picture of the biting snake for identification) at the Chemolingot and Mwingi sub-county hospitals in Baringo and Kitui counties, central Kenya. Common local and systemic features on admission included pain (n=15, 100%), swelling (n=14, 93%), and haemorrhage (n=9, 60%). Coagulopathy (n=2, 13%), blistering (n=1, 8%) and shock (n=1, 8%) were less common. In addition, we conducted a literature review and identified 23 studies with detailed descriptions of the clinical features of puff adder envenoming from 37 patients. Local features were common and consistent across cases-swelling (100%, n=37) and pain (95%, n=35). Systemic features were less consistent, with 10 (27%) patients exhibiting hypotension on admission, 10 (27%) patients reporting a fever, and 13 (35%) developing anaemia. Some complications were more common in patients with bites by captive snakes (amputations), compared to patients with bites by wild snakes (hypotension). Snake identification was easier and more accurate after bites by captive snakes, but more challenging for patients bitten in community settings.

We combined clinical cases and a literature review to describe the common and less common clinical features of puff adder envenoming. Further clinical research incorporating serial laboratory assays of patients with definitively identified puff adder bites is crucial to better understand the pathophysiology of envenoming by this medically important snake species.

C-type lectins (CTLs) act as pattern recognition receptors (PRRs) to initiate the innate immune response in insects. A CTL with dual carbohydrate recognition domains (CRDs) (named immulectin-4 [IML-4]) was selected from the Ostrinia furnacalis transcriptome dataset for functional studies. We cloned the full-length complementary DNA of O. furnacalis IML-4 (OfIML-4). It encodes a 328-residue protein with a Glu-Pro-Asn (EPN) and Gln-Pro-Asp (QPD) motifs in 2 CRDs, respectively. OfIML-4 messenger RNA levels increased significantly upon the bacterial and fungal infection. Recombinant OfIML-4 (rIML-4) and its individual CRDs (rCRD1 and rCRD2) exhibited the binding ability to various microorganisms including Escherichia coli, Micrococcus luteus, Pichia pastoris, and Beauveria bassiana, and the cell wall components including lipopolysaccharide from E. coli, peptidoglycan from M. luteus or Bacillus subtilis, and curdlan from Alcaligenes faecalis. The binding further induced the agglutination of E. coli, M. luteus, and B. bassiana in the presence of calcium, the phagocytosis of Staphylococcus aureus by the hemocytes, in vitro encapsulation and melanization of nickel-nitrilotriacetic acid beads, and a significant increase in phenoloxidase activity of plasma. In addition, rIML-4 significantly enhanced the phagocytosis, nodulation, and resistance of O. furnacalis to B. bassiana. Taken together, our results suggest that OfIML-4 potentially works as a PRR to recognize the invading microorganisms, and functions in the innate immune response in O. furnacalis.

The inflammatory response triggered by Toll-like receptors (TLRs) may implicated in the development of the pathogenesis of adult-onset Still's disease (AOSD). This study evaluated the efficacy of TLR inhibitor peptides, specifically TLR inhibitor peptide 1 (TIP-1) and MAL/MyD88 inhibitory peptide 2 (MIP-2) in animal models of AOSD. THP-1 cells were stimulated with TLR agonists and treated with TIP-1 or MIP-2. Interferon (IFN)-γ knock-out mice were induced with AOSD-like symptoms using Mycobacterium mixed with Freund's complete adjuvant (CFA), then treated with the peptides. THP-1 cells treated with TIP-1 and MIP-2 showed significantly decreased expression of TLRs agonist-induced MyD88 and phosphorylated NF-κB, except TLR9 agonists. Furthermore, the peptides resulted in a significant decrease in the concentrations of interleukin (IL)-1β and IL-6 in the culture supernatants, except TLR9 agonists. In animal models of AOSD, treatment with inhibitor peptides significantly improved their clinical symptoms. The administration of these peptides resulted in a significant decrease in serum levels of IL-1β and IL-18. The expression of inflammatory cytokines were downregulated in the spleen and lymph node of TIP-1 and MIP-2 treated mice. These findings suggest that TIP-1 and MIP-2 may be effective candidates for AOSD treatment, as they have broad specificity for TLRs.

Available evidence illustrates that microbiome is a promising target for the study of growth, diagnosis and therapy of various types of cancer. Lung cancer is a leading cause of cancer death worldwide. The relationship of microbiota and their products with diverse pathologic conditions has been getting large attention. The novel research suggests that the microbiome plays an important role in the growth and progression of lung cancer. The lung microbiome plays a crucial role in maintaining mucosal immunity and synchronizing the stability between tolerance and inflammation. Alteration in microbiome is identified as a critical player in the progression of lung cancer and negatively impacts the patient. Studies suggest that healthy microbiome is essential for effective therapy. Various clinical trials and research are focusing on enhancing the treatment efficacy by altering the microbiome. The regulation of microbiota will provide innovative and promising treatment strategies for the maintenance of host homeostasis and the prevention of lung cancer in lung cancer patients. In the current review article, we presented the latest progress about the involvement of microbiome in the growth and diagnosis of lung cancer. Furthermore, we also assessed the therapeutic status of the microbiome for the management and treatment of lung cancer.

The liver plays a central role in fat storage, but little is known about physiological fat accumulation during early development. Here we investigated a transient surge in hepatic lipid droplets observed in newborn mice immediately after birth. We developed a novel model to quantify liver fat content without tissue processing. Using high-resolution microscopy assessed the spatial distribution of lipid droplets within hepatocytes. Lugol's iodine staining determined the timing weaning period, and milk deprivation experiments investigated the relationship between milk intake and fat accumulation. Lipidomic analysis revealed changes in the metabolic profile of the developing liver. Finally, we investigated the role of Toll-like receptor 4 (TLR4) signaling in fat storage using knockout mice and cell-specific deletion strategies. Newborn mice displayed a dramatic accumulation of hepatic lipid droplets within the first 12 h after birth, persisting for the initial two weeks of life. This pattern coincided with exclusive milk feeding and completely abated by the third week, aligning with weaning. Importantly, the observed fat accumulation shared characteristics with established models of pathological steatosis, suggesting potential biological relevance. Lipid droplets were primarily localized within the cytoplasm of hepatocytes. Milk deprivation experiments demonstrated that milk intake is the primary driver of this transient fat accumulation. Lipidomic analysis revealed significant changes in the metabolic profile of newborn livers compared to adults. Interestingly, several highly abundant lipids in newborns were identified as putative ligands for TLR4. Subsequent studies using TLR4-deficient mice and cell-specific deletion revealed that TLR4 signaling, particularly within hepatocytes, plays a critical role in driving fat storage within the newborn liver. Additionally, a potential collaboration between metabolic and immune systems was suggested by the observed effects of myeloid cell-specific TLR4 ablation. This study demonstrates a unique phenomenon of transient hepatic fat accumulation in newborn mice driven by milk intake and potentially regulated by TLR4 signaling, particularly within hepatocytes.

As the first line of host immune defense, innate immunity plays a key role in warding off foreign pathogens and damage. Drosophila melanogaster, as a classical model animal for more than 100 years, is an important research model for studying innate immunity. In recent years, scientists have made remarkable progress in the recognition mechanisms of innate immunity, the mechanisms of effector molecules, and the modes of their response at the cellular and tissue levels. However, the interaction between innate immunity and other physiological functions remains relatively novel and has yet to be systematically explored. Here, we first briefly discuss the link between the innate immunity system and physiological regulation, from several representative perspectives such as sleep, insulin, and brain function. Then, using Drosophila as a model, we provide an overview of the physiological system and specifically summarize the research on the regulation of physiology by innate immunity, covering sleep, lipid metabolism, development, neurodegenerative diseases, memory, feeding, lifespan, movement, and antioxidation. This review provides valuable perspectives into how innate immunity influences other physiological processes, providing a deeper understanding of the complex roles underlying innate immunity.

Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.

This study aimed to evaluate alternative in vivo treatment trials using natural products for ectoparasitic infestation on Nile tilapia; these two products were not previously used in the treatment of parasitic fish diseases. So, a total of 400 Oreochromis niloticus (O. niloticus) fish measured 10-15 cm in length; 350 from a fish farm in (Kafr Elsheikh and 50 from Nile River (Al Bahr Al Aazam), Egypt. The examined fishes were 10-15 ± 0.5 cm long and weighed from 45 g ± 5. The collected fish were examined for different clinical abnormalities. Each part of the fish underwent a careful microscopic examination of mucous surrounding the skin; gills and fins. Two feed supplements were used experimentally to decrease mortality and treat fish against ectoparasites (Herb-All PARA-X® and Herb-All CALM®). Total mRNA was extracted from the gills of different examined groups. Glucose; nitric oxide; cortisol as well as lysozyme activity were assessed in all groups. The gills of the examined fish were collected for histopathological examination. Only, Dactyolgyrus sp. was recovered. The intensity of the parasite was counted per microscopic field. The treated groups showed low levels of the parameters compared to the control positive group. Up-regulation of both Tumor necrosis factor-α (TNF- α) and heat shock protein 70 (hsp-70) were detected in fins, gills, and skin in the infested tilapia. The treatment and prophylaxis significantly downregulated both genes in the studied organ in a dose-dependent manner. Recorded lesions which were scored according to their severity. In conclusion; following the use of those products, fish health has been greatly improved and that is indicated by findings of immune reactions as well as histopathology.

Previous researches have suggested an important association between gut microbiota (GM) and vascular pathologies such as atherosclerosis. This study aimed to explore the association between 196 GM taxa and retinal vein occlusion (RVO).

This study used Mendelian randomization (MR), linkage disequilibrium score regression (LDSC), and polygenic overlap analysis. Genome-wide association study (GWAS) data associated with 196 GM taxa was obtained from the MiBioGen consortium, involving a large number of European-ancestry participants. GWAS data of RVO was obtained from the FinnGen consortium and another study that also involved European-ancestry participants. Inverse-variance weighted was used as the primary approach for MR estimation. Moreover, LDSC and polygenic overlap analyses were performed to evaluate the genetic correlation between GM taxa and RVO.

The MR results identified the association of six GM taxa, including class Bacilli, order Lactobacillales, family Streptococcaceae, genus Clostridium innocuum group, genus Family XIII AD3011 group, and genus Subdoligranulum with the development of RVO. In addition, the polygenic overlap analysis supported the genetic association between GM and RVO.

Our findings confirmed the association between six GM taxa and the development of RVO, thereby highlighting the effects of GM on retinal vascular health.

The results may provide the rationale for developing GM-based strategies for preventing the onset of RVO.

Cardiovascular diseases (CVDs) are a major cause of morbidity and mortality worldwide and there are strong links existing between gut health and cardiovascular health. Gut microbial diversity determines gut health. Dysbiosis, described as altered gut microbiota, causes bacterial translocations and abnormal gut byproducts resulting in systemic inflammation.

To review the current literature on the relationships between gut microbiota, dysbiosis, and CVD development, and explore therapeutic methods to prevent dysbiosis and support cardiovascular health.

Dysbiosis increases levels of pro-inflammatory substances while reducing those of anti-inflammatory substances. This accumulative inflammatory effect negatively modulates the immune system and promotes vascular dysfunction and atherosclerosis. High Firmicutes to Bacteroidetes ratios, high trimethylamine-n-oxide to short-chain fatty acid ratios, high indole sulfate levels, low cardiac output, and polypharmacy are all associated with worse cardiovascular outcomes. Supplementation with prebiotics and probiotics potentially alleviates some CVD risk. Blood and stool samples may be used in clinical practice to quantify and qualify gut bacterial ratios and byproducts, assess patients' risk for adverse cardiovascular outcomes, and track their gut health progress. Further research is required to set population-based cutoffs for normal and abnormal gut microbiota and byproduct ratios.

The generation of hypothyroid and hyperthyroid mouse models is one of the approaches used to investigate the complex interplay between thyroid hormones and the immune system. We present a detailed protocol describing how to induce endotoxic shock by lipopolysaccharide (LPS) administration, and how to investigate the role of immune populations, specifically macrophages, responding to endotoxemia.This book chapter provides the use of different molecular techniques, such as Western Blotting, Immunohistochemistry, q-PCR, Luciferase assays, or ChIP assays, with which researchers can gain valuable insights into the immune system's interaction with hormonal signaling pathways, for instance, examining the effect of thyroid hormones on signaling of STAT3, NF-κB, and ERK in response to LPS, and inflammatory mediators, such as interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNFα) within these cells. The signaling pathways involved and the exploration of the relationship between thyroid hormones and the immune system can be analyzed using several molecular biology technologies in order to clarify their interplay in various disease states.

C-type lectins (CTLs), as a large family of pattern recognition receptors (PRRs), have been reported to be involved in bacterial infection, but the role of CTLs in development has been poorly understood in insects. The orthologues of Tribolium castaneum CTL9 (TcCTL9) have been identified among insects, but its functions were currently unclear. Therefore, we performed functional analysis of TcCTL9 in this study. Our results indicated that TcCTL9 could bind to bacteria through lipopolysaccharide and peptidoglycan, and agglutinate Gram-positive and Gram-positive bacteria in a Ca2+-dependent manner. Silencing TcCTL9 reduced the immune resistance to Staphylococcus aureus and Escherichia coli, decreased the expression of antimicrobial peptides and prophenoloxidase, and inhibited the phenoloxidase activity. These data suggested that TcCTL9 functioned in the immune response via the Toll and IMD pathways and prophenoloxidase system. During development, TcCTL9 had high expression in the periods of egg to larva and pupa to adult, and knockdown of TcCTL9 suppressed the metamorphosis, egg production and hatchability, and ovary development through ecdysone and juvenile hormone pathways in T. castaneum. This study comprehensively clarified the functions of TcCTL9 orthologues in insects and provided the theoretical basis for developing novel targets of pesticides.

Tank-binding kinase 1 (TBK1) is a critical signal transducer in the nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) pathways, essential for innate immunity. However, its negative regulation mechanisms remain unclear. This study demonstrates that TBK1 succinylation, regulated by desuccinylase SIRT5, inhibits lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4)-mediated NF-κB and IRF signaling activation. We identified three key succinylation sites on TBK1: K38, K154, and K692. In endotoxemia and sepsis models, reduced SIRT5 levels in macrophages increased TBK1 succinylation, inhibiting its binding to IRF3 and TRAF2 and suppressing the inflammatory response. In vivo, adoptive transfer of macrophages expressing the succinylation-resistant TBK1-2KR (K154/692R) mutant reversed the inflammatory cytokine suppression caused by SIRT5 deficiency, exacerbating sepsis-induced lung injury. These findings reveal a novel mechanism by which SIRT5 modulates TBK1 activity and macrophage-mediated inflammation during sepsis.

During virus infection, the activation of the antiviral endoribonuclease, ribonuclease L (RNase L), by a unique ligand 2'-5'-oilgoadenylate (2-5A) causes the cleavage of single-stranded viral and cellular RNA targets, restricting protein synthesis, activating stress response pathways, and promoting cell death to establish broad antiviral effects. The immunostimulatory dsRNA cleavage products of RNase L activity (RL RNAs) recruit diverse dsRNA sensors to activate signaling pathways to amplify interferon (IFN) production and activate inflammasome, but the sensors that promote cell death are not known. In this study, we found that DEAH-box polypeptide 15 (DHX15) and retinoic acid-inducible gene I (Rig-I) are essential for apoptosis induced by RL RNAs and require mitochondrial antiviral signaling (MAVS), c-Jun amino terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) for caspase-3-mediated intrinsic apoptosis. In RNase L-activated cells, DHX15 interacts with Rig-I and MAVS, and cells lacking MAVS expression were resistant to apoptosis. RL RNAs induced the transcription of genes for IFN and proinflammatory cytokines by interferon regulatory factor 3 (IRF-3) and nuclear factor kB (NF-kB), while cells lacking both DHX15 and Rig-I showed a reduced induction of cytokines. However, apoptotic cell death is independent of both IRF-3 and NF-kB, suggesting that cytokine and cell death induction by RL RNAs are uncoupled. The RNA binding of both DHX15 and Rig-I is required for apoptosis induction, and the expression of both single proteins in cells lacking both DHX15 and Rig-I is insufficient to promote cell death by RL RNAs. Cell death induced by RL RNAs suppressed Coxsackievirus B3 (CVB3) replication, and inhibiting caspase-3 activity or cells lacking IRF-3 showed that the induction of apoptosis directly resulted in the CVB3 antiviral effect, and the effects were independent of the role of IRF-3.

Type Ι interferon (IFN) production mediated by retinoic acid-inducible gene 1 (RIG-I) and mitochondrial antiviral signaling protein (MAVS) is essential for antiviral innate immune responses. Here, we report the identification of a novel co-sensor for cytosolic nucleic acids: DEAD/H-box helicase 11 (DDX11), a member of the DExD/H (Asp-Glu-x-Asp/His)-box helicase family. Knockdown or knockout of DDX11 attenuated the ability of cells to increase IFN-β, IFN-stimulated gene 56, and C-X-C motif chemokine ligand 10 in response to SeV and poly (I:C) by blocking the activation of TANK-binding kinase 1 and IFN regulatory factor 3. Nucleic acid sensing by DDX11 was independent of the stimulator of IFN genes but was dependent on RIG-I and MAVS. DDX11 regulated RIG-I-MAVS-mediated IFN signaling by specifically interacting with nucleic acid, RIG-I, and MAVS to enhance RIG-I-double-strand RNA and RIG-I-MAVS binding affinity. Overall, our results identified a critical role for DDX11 in the innate immune response and provided molecular insights into the mechanisms by which DDX11 recognized cytosolic nucleic acid and interacted with RIG-Ι and MAVS for potent IFN signaling and antiviral immunity.

Innate immunity is the first and most rapid host defense against virus infection. Recognition of viral RNA by the retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs) initiates innate antiviral immune responses. How the binding of viral RNA to and activation of the RLRs are regulated remains enigmatic. In this study, we identified DEAD/H-box helicase 11 (DDX11) as a positive regulator of the RIG-I-mitochondrial antiviral signaling protein (MAVS)-mediated signaling pathways. Mechanistically, we demonstrated that DDX11 bound to viral RNA, interacted with RIG-I, and promoted their binding to viral RNA. DDX11 also promoted the interaction between RIG-I and MAVS and activation of RIG-I-MAVS signaling. Overall, our results elucidate the role of DDX11 in RIG-I-MAVS-dependent signaling pathways and may shed light on innate immune gene regulation.

Bacterial cyclic dinucleotides (CDNs), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) upregulate interferon signaling proteins of human gingival fibroblasts (HGFs). However, the simultaneous effect of bacterial CDNs and lipopolysaccharides (LPS) on the HGF proteome is unknown.

The aim was to apply an unbiased proteomics approach to evaluate how simultaneous exposure to CDNs and Porphyromonas gingivalis (Pg) LPS affect the global proteome of HGFs.

The proteomic responses of HGFs were examined under three different treatment conditions (c-di-AMP+Pg LPS, c-di-GMP+Pg LPS, and Pg LPS alone) by label-free quantitative mass spectrometry analysis.

Simultaneous exposure to CDNs and Pg LPS significantly upregulated innate immunity-related and interferon signaling-related proteins, such as ubiquitin-like protein ISG15 (ISG15), deoxynucleoside triphosphate triphosphohydrolase (SAMHD1), interferon regulatory factor 9 (IRF-9), interferon-induced GTP-binding protein Mx (MX)1, and MX2. Interferon signaling pathway was the most significantly regulated canonical pathway in both CDN treatment groups.

Simultaneous exposure to CDNs and Pg LPS stimulates the periodontal immune response by activating the anti-microbial cellular responses of HGFs with some notable differences from individual exposures.

The aim of the research is to increase the applicability of lipopeptides as drugs. To this end, non-ionic triblock copolymers, namely poloxamers, were applied. The physico-chemical properties of poloxamers vary depending on the length of the blocks. In our study, we experimented with different types and systematically investigated the variation of the critical micelle concentration (CMC) of poloxamers at 25 and 37 °C in different media. In addition, the cytotoxicity of the different poloxamer micelles on three different cell lines was evaluated, and based on the results, Plur104, Plur123, and Plur127 were selected. Fatty acid elongated derivatives of a short antibacterial peptide (pL1), a medium-sized anticancer peptide (pCM15), and a branched-chain vaccine antigen (pATIPC) were used as lipopeptide models, and their formulations with the selected poloxamers were investigated. The solubility and homogeneity of the lipopeptides were significantly increased, and dynamic light scattering (DLS) measurements showed the formation of small particles of around 20 nm, which were well reproducible and storable. Similar homogenous micelle formation was observed after freeze-drying and reconstitution with water. The pL1 lipopeptide, formulated with the selected poloxamers, exhibited enhanced antibacterial activity with significantly reduced haemolytic side effects. The pCM15 peptide, when incorporated into poloxamer micelles, showed significantly enhanced cytotoxicity against tumor cells. Additionally, the internalization rate of poloxamer-formulated pATIPC peptide by antigen-presenting model cells exceeded that of the unformulated peptide. Our results demonstrate the potential of poloxamers as promising tools for the formulation of lipopeptides and for the optimization of their selectivity.

To evaluate the risk of neutropenia during treatment with anti-IL-23 antibodies in patients with psoriasis.

We conducted an observational study with cohort design using MID-NET® in Japan. We identified patients with psoriasis who were newly prescribed anti-IL-23 antibodies, anti-IL-17-antibodies, adalimumab, or apremilast between January 1, 2009, and March 31, 2021. We estimated the adjusted hazard ratio (aHR) of anti-IL-23 antibodies compared to that of anti-IL-17 antibodies, adalimumab, or apremilast, for the risk of grade 2 (neutrophil count < 1,500/μL) or grade 3 (neutrophil count < 1,000/μL) neutropenia.

Overall, 287 patients on anti-IL-23 antibodies, 189 patients on anti-IL-17 antibodies, 293 patients on adalimumab, and 540 patients on apremilast were included. Compared with anti-IL-17 antibodies, the aHR (95% confidence interval (CI)) of anti-IL-23 antibodies was 0.83 (0.27-2.51) for grade 2 and 0.40 (0.02-7.60) for grade 3 neutropenia; that when compared with adalimumab was 0.76 (0.28-2.06) for grade 2 but was not calculated for grade 3 as no cases were found; and that compared with apremilast was 3.88 (0.62-24.48) for grade 2 and 0.43 (0.02-11.63) for grade 3 neutropenia.

No clear increase in the risk of neutropenia with anti-IL-23 antibodies was observed.