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Wang W, Dai C, Zhu P, Wu M, Zhang H, Wei Q, Zhou T, Tan X, Jiang Y, Cheng X, Liang Z, Wu X, Chen Z, Weng X. Liver transplant-facilitated CD161 +Vα7.2 + MAIT cell recovery demonstrates clinical benefits in hepatic failure patients. Nat Commun 2025; 16:4022. [PMID: 40301342 PMCID: PMC12041255 DOI: 10.1038/s41467-025-59308-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 04/18/2025] [Indexed: 05/01/2025] Open
Abstract
Mucosal-associated invariant T (MAIT) cells exert multifaceted effects such as anti-microbial activity, tissue repair, and pro-fibrotic effects across various disease settings. Nonetheless, their role in liver injury and hemostasis remains debated. Here, we report a significant depletion and functional dysregulation of MAIT cells, which is associated with disease severity and accumulated bile acids in HBV-infected patients with varying degree of liver injury. Liver transplantation facilitates a gradual recovery of recipient-originated MAIT cells. Transcriptome analysis reveals enhanced MAIT cell activation, while TCR mining demonstrates clonotype overlap between circulating and hepatic MAIT cells during significant liver injury. TCR-activated MAIT cells from transplant recipients display higher protective capacity but reduced pathological potential than those from liver failure patients. Compromised recovery of MAIT cells is linked to post-transplantation complications, whereas prompt recovery predicates favorable clinical outcome. These findings underscore the intricate interplay between MAIT cells and the hepatic environment, highlighting MAIT cells as potential therapeutic targets and sensitive predictors for clinical outcome in individuals experiencing liver failure and post liver transplantation.
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Affiliation(s)
- Wei Wang
- Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Chen Dai
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences; Organ Transplantation Clinical Medical Research Center of Hubei Province, Wuhan, China
| | - Peng Zhu
- Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mi Wu
- Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Haoquan Zhang
- Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qing Wei
- Department of Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ting Zhou
- Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaosheng Tan
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences; Organ Transplantation Clinical Medical Research Center of Hubei Province, Wuhan, China
| | - Ying Jiang
- Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Xue Cheng
- Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Zhihui Liang
- Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Xiongwen Wu
- Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
| | - Zhishui Chen
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences; Organ Transplantation Clinical Medical Research Center of Hubei Province, Wuhan, China.
| | - Xiufang Weng
- Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China.
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences; Organ Transplantation Clinical Medical Research Center of Hubei Province, Wuhan, China.
- Department of Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Walkenhorst M, Sonner JK, Meurs N, Engler JB, Bauer S, Winschel I, Woo MS, Raich L, Winkler I, Vieira V, Unger L, Salinas G, Lantz O, Friese MA, Willing A. Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis. Nat Commun 2024; 15:9287. [PMID: 39468055 PMCID: PMC11519641 DOI: 10.1038/s41467-024-53657-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Accepted: 10/18/2024] [Indexed: 10/30/2024] Open
Abstract
Mucosal-associated invariant T (MAIT) cells express semi-invariant T cell receptors (TCR) for recognizing bacterial and yeast antigens derived from riboflavin metabolites presented on the non-polymorphic MHC class I-related protein 1 (MR1). Neuroinflammation in multiple sclerosis (MS) is likely initiated by autoreactive T cells and perpetuated by infiltration of additional immune cells, but the precise role of MAIT cells in MS pathogenesis remains unknown. Here, we use experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, and find an accumulation of MAIT cells in the inflamed central nervous system (CNS) enriched for MAIT17 (RORγt+) and MAIT1/17 (T-bet+RORγt+) subsets with inflammatory and protective features. Results from transcriptome profiling and Nur77GFP reporter mice show that these CNS MAIT cells are activated via cytokines and TCR. Blocking TCR activation with an anti-MR1 antibody exacerbates EAE, whereas enhancing TCR activation with the cognate antigen, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil, ameliorates EAE severity, potentially via the induction of amphiregulin (AREG). In summary, our findings suggest that TCR-mediated MAIT cell activation is protective in CNS inflammation, likely involving an induction of AREG.
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Affiliation(s)
- Mark Walkenhorst
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jana K Sonner
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Nina Meurs
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jan Broder Engler
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Simone Bauer
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ingo Winschel
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marcel S Woo
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lukas Raich
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Iris Winkler
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Vanessa Vieira
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lisa Unger
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Gabriela Salinas
- NGS-Integrative Genomics Core Unit, Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany
| | - Olivier Lantz
- Institut National de la Santé et de la Recherche Médicale U932, PSL University, Institut Curie, Paris, France
| | - Manuel A Friese
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Anne Willing
- Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Samer C, McWilliam HEG, McSharry BP, Burchfield JG, Stanton RJ, Rossjohn J, Villadangos JA, Abendroth A, Slobedman B. Impaired endocytosis and accumulation in early endosomal compartments defines herpes simplex virus-mediated disruption of the nonclassical MHC class I-related molecule MR1. J Biol Chem 2024; 300:107748. [PMID: 39260697 PMCID: PMC11736056 DOI: 10.1016/j.jbc.2024.107748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 08/13/2024] [Accepted: 08/21/2024] [Indexed: 09/13/2024] Open
Abstract
Presentation of metabolites by the major histocompatibility complex class I-related protein 1 (MR1) molecule to mucosal-associated invariant T cells is impaired during herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections. This is surprising given these viruses do not directly synthesise MR1 ligands. We have previously identified several HSV proteins responsible for rapidly downregulating the intracellular pool of immature MR1, effectively inhibiting new surface antigen presentation, while preexisting ligand-bound mature MR1 is unexpectedly upregulated by HSV-1. Using flow cytometry, immunoblotting, and high-throughput fluorescence microscopy, we demonstrate that the endocytosis of surface MR1 is impaired during HSV infection and that internalized molecules accumulate in EEA1-labeled early endosomes, avoiding degradation. We establish that the short MR1 cytoplasmic tail is not required for HSV-1-mediated downregulation of immature molecules; however it may play a role in the retention of mature molecules on the surface and in early endosomes. We also determine that the HSV-1 US3 protein, the shorter US3.5 kinase and the full-length HSV-2 homolog, all predominantly target mature surface rather than total MR1 levels. We propose that the downregulation of intracellular and cell surface MR1 molecules by US3 and other HSV proteins is an immune-evasive countermeasure to minimize the effect of impaired MR1 endocytosis, which might otherwise render infected cells susceptible to MR1-mediated killing by mucosal-associated invariant T cells.
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Affiliation(s)
- Carolyn Samer
- Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
| | - Hamish E G McWilliam
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia
| | - Brian P McSharry
- Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia; School of Dentistry and Medical Sciences, Faculty of Science and Health, and Gulbali Institute, Charles Sturt University, Wagga Wagga, New South Wales, Australia
| | - James G Burchfield
- Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia; School of Life and Environmental Sciences, The University of Sydney, Camperdown, New South Wales, Australia
| | - Richard J Stanton
- Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, Wales, UK
| | - Jamie Rossjohn
- Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, Wales, UK; Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
| | - Jose A Villadangos
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia
| | - Allison Abendroth
- Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
| | - Barry Slobedman
- Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia.
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Wu S, Yang X, Lou Y, Xiao X. MAIT cells in bacterial infectious diseases: heroes, villains, or both? Clin Exp Immunol 2023; 214:144-153. [PMID: 37624404 PMCID: PMC10714195 DOI: 10.1093/cei/uxad102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 08/20/2023] [Accepted: 08/21/2023] [Indexed: 08/26/2023] Open
Abstract
Due to the aggravation of bacterial drug resistance and the lag in the development of new antibiotics, it is crucial to develop novel therapeutic regimens for bacterial infectious diseases. Currently, immunotherapy is a promising regimen for the treatment of infectious diseases. Mucosal-associated invariant T (MAIT) cells, a subpopulation of innate-like T cells, are abundant in humans and can mount a rapid immune response to pathogens, thus becoming a potential target of immunotherapy for infectious diseases. At the site of infection, activated MAIT cells perform complex biological functions by secreting a variety of cytokines and cytotoxic substances. Many studies have shown that MAIT cells have immunoprotective effects because they can bridge innate and adaptive immune responses, leading to bacterial clearance, tissue repair, and homeostasis maintenance. MAIT cells also participate in cytokine storm generation, tissue fibrosis, and cancer progression, indicating that they play a role in immunopathology. In this article, we review recent studies of MAIT cells, discuss their dual roles in bacterial infectious diseases and provide some promising MAIT cell-targeting strategies for the treatment of bacterial infectious diseases.
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Affiliation(s)
- Sihong Wu
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Xi Yang
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Yongliang Lou
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Xingxing Xiao
- Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
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Mehta H, Tasin I, Hackstein CP, Willberg C, Klenerman P. Prostaglandins differentially modulate mucosal-associated invariant T-cell activation and function according to stimulus. Immunol Cell Biol 2023; 101:262-272. [PMID: 36541521 PMCID: PMC10152717 DOI: 10.1111/imcb.12617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 05/29/2022] [Accepted: 12/20/2022] [Indexed: 12/24/2022]
Abstract
Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell type conserved in many mammals and especially abundant in humans. Their semi-invariant T-cell receptor (TCR) recognizes the major histocompatibility complex-like molecule MR1 presenting riboflavin intermediates associated with microbial metabolism. Full MAIT cell triggering requires costimulation via cytokines, and the cells can also be effectively triggered in a TCR-independent manner by cytokines [e.g. interleukin (IL)-12 and IL-18 in combination]. Thus, triggering of MAIT cells is highly sensitive to local soluble mediators. Suppression of MAIT cell activation has not been well explored and could be very relevant to their roles in infection, inflammation and cancer. Prostaglandins (PG) are major local mediators of these microenvironments which can have regulatory roles for T cells. Here, we explored whether prostaglandins suppressed MAIT cell activation in response to TCR-dependent and TCR-independent signals. We found that protaglandin E2 (PGE2 ) and to a lesser extent protaglandin D2 (PGD2 ), but not leukotrienes, suppressed MAIT cell responses to Escherichia coli or TCR triggers. However, there was no impact on cytokine-induced triggering. The inhibition was blocked by targeting the signaling mediated via PG receptor 2 (PTGER2) and 4 (PTGER4) receptors in combination. These data indicate that prostaglandins can potentially modulate local MAIT cell functions in vivo and indicate distinct regulation of the TCR-dependent and TCR-independent pathways of MAIT cell activation.
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Affiliation(s)
- Hema Mehta
- The Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUK
| | - Irene Tasin
- The Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUK
| | | | - Christian Willberg
- The Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUK
| | - Paul Klenerman
- The Peter Medawar Building for Pathogen ResearchUniversity of OxfordOxfordUK
- NIHR Biomedical Research CentreUniversity of OxfordOxfordUK
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Gherardin NA, Legoux F, Consonni M, Paget C. CD1 and MR1: An update after a long-awaited reunion. Immunity 2022; 55:2211-2216. [PMID: 36516812 DOI: 10.1016/j.immuni.2022.11.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/10/2022] [Accepted: 11/17/2022] [Indexed: 12/14/2022]
Abstract
CD1 molecules and the MHC-related protein 1 (MR1) present lipid and small molecule antigens, respectively, for T cell surveillance. The biology of these molecules, the antigens they present, and the T cells that respond to them were recently discussed during the 12th International CD1-MR1 Meeting held in Gothenburg, Sweden.
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Affiliation(s)
- Nicholas A Gherardin
- Department of Microbiology & Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, VIC 3000, Australia.
| | - Francois Legoux
- INSERM ERL1305, CNRS UMR6290, Université de Rennes 1, Institut de Génétique & Développement de Rennes, France
| | - Michela Consonni
- Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan 20132, Italy
| | - Christophe Paget
- Centre d'Etude des Pathologies Respiratoires, INSERM U1100, Université de Tours, Faculté de Médecine de Tours, 37000, Tours, France
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7
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Improved MAIT cell functions following fecal microbiota transplantation for metastatic renal cell carcinoma. Cancer Immunol Immunother 2022; 72:1247-1260. [PMID: 36396738 PMCID: PMC9672546 DOI: 10.1007/s00262-022-03329-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 11/09/2022] [Indexed: 11/19/2022]
Abstract
Strategies to modify the gut microbiome in cancer patients using fecal microbiota transplantation (FMT) have gained momentum as a therapeutic intervention. However, how FMT impacts innate-like, antimicrobial T lymphocytes is unclear. In this study, we assessed peripheral blood (PB) mucosa-associated invariant T (MAIT) cell frequencies and functions in patients with metastatic renal cell carcinoma (mRCC) before and seven days after they received FMT as part of a clinical trial. We found comparable MAIT cell frequencies in healthy controls and mRCC patients. In contrast, γδ T cells exhibited a numerical decline in mRCC, which was partially reversed by FMT. We also found a significant increase in the PB CD4+ MAIT cell compartment of mRCC patients with or without FMT. Paired sample analyses revealed CD69 upregulation on MAIT cells accompanied by decreased PD-1 levels post-FMT. These changes were unique to MAIT cells as non-MAIT T lymphocytes showed either no trend or a trend in the opposite direction. Importantly, FMT did not render MAIT cells exhausted as also judged by their stable expression of TIM-3, LAG-3, BTLA, CTLA-4, TIGIT and VISTA. These findings were corroborated in functional assays in which MAIT cells were stimulated with MR1 ligands or with a combination of IL-12 and IL-18 to produce inflammatory cytokines and granzyme B. Indeed, when stimulated ex vivo with IL-12 and IL-18, MAIT cells mounted a more rigorous TNF-α response post-FMT. In conclusion, FMT improves MAIT cell functions, which should serve patients well in subsequent microbial challenges in the face of cancer-elicited immunosuppression. Trial Registration: https://clinicaltrials.gov/ Identifier: NCT04163289 (registration date: November 14, 2019).
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Boonpattanaporn N, Kongkaew T, Sengprasert P, Souter MNT, Lakananurak N, Rerknimitr R, Corbett AJ, Reantragoon R. Human mucosal Vα7.2 + CD161 hi T cell distribution at physiologic state and in Helicobacter pylori infection. J Leukoc Biol 2022; 112:717-732. [PMID: 35704477 DOI: 10.1002/jlb.4a0421-223rr] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 05/23/2022] [Indexed: 01/02/2023] Open
Abstract
Mucosal-associated invariant T (MAIT) cells are innate-like, unconventional T cells that are present in peripheral blood and mucosal surfaces. A clear understanding of how MAIT cells in the mucosae function and their role in host immunity is still lacking. Therefore, our aim was to investigate MAIT cell distribution and their characteristics in the gastrointestinal (GI) mucosal tissue based on Vα7.2+ CD161hi identification. We showed that Vα7.2+ CD161hi T cells are present in both intraepithelial layer and lamina propriae of the GI mucosa, but have different abundance at each GI site. Vα7.2+ CD161hi T cells were most abundant in the duodenum, but had the lowest reactivity to MR1-5-OP-RU tetramers when compared with Vα7.2+ CD161hi T cells at other GI tissue sites. Striking discrepancies between MR1-5-OP-RU tetramer reactive cells and Vα7.2+ CD161hi T cells were observed along each GI tissue sites. Vα7.2+ CD161hi TCR repertoire was most diverse in the ileum. Similar dominant profiles of TRBV usage were observed among peripheral blood, duodenum, ileum, and colon. Some TRBV chains were detected at certain intestinal sites and not elsewhere. The frequency of peripheral blood Vα7.2+ CD161hi T cells correlated with mucosal Vα7.2+ CD161hi T cells in lamina propriae ileum and lamina propriae colon. The frequency of peripheral blood Vα7.2+ CD161hi T cells in Helicobacter pylori-infected individuals was significantly lower than uninfected individuals, but this was not observed with gastric Vα7.2+ CD161hi T cells. This study illustrates the biology of Vα7.2+ CD161hi T cells in the GI mucosa and provides a basis for understanding MAIT cells in the mucosa and MAIT-related GI diseases.
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Affiliation(s)
- Norasate Boonpattanaporn
- Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand
| | - Thidarat Kongkaew
- Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand
| | - Panjana Sengprasert
- Immunology Division, Faculty of Medicine, Department of Microbiology, Chulalongkorn University, Bangkok, Thailand
| | - Michael N T Souter
- Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
| | - Narisorn Lakananurak
- Faculty of Medicine, Department of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Rungsun Rerknimitr
- Faculty of Medicine, Department of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Alexandra J Corbett
- Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
| | - Rangsima Reantragoon
- Immunology Division, Faculty of Medicine, Department of Microbiology, Chulalongkorn University, Bangkok, Thailand.,Faculty of Medicine, Center of Excellence in Immunology and Immune-Mediated Diseases, Chulalongkorn University, Bangkok, Thailand.,Faculty of Medicine, Center of Excellence in Skeletal Disorders and Enzyme Reaction Mechanism, Chulalongkorn University, Bangkok, Thailand
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Mehta H, Lett MJ, Klenerman P, Filipowicz Sinnreich M. MAIT cells in liver inflammation and fibrosis. Semin Immunopathol 2022; 44:429-444. [PMID: 35641678 PMCID: PMC9256577 DOI: 10.1007/s00281-022-00949-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 05/06/2022] [Indexed: 02/07/2023]
Abstract
Mucosal-associated invariant T cells or MAIT cells are an abundant cell type in humans and especially so in the liver. MAIT cells are a subset of T lymphocytes that sit at a bridge between innate and adaptive immunity, so-called innate-like or "unconventional" T cells. The specificity of their antigen receptor (T cell receptor or TCR) is for the conserved major histocompatibility complex (MHC)-related molecule MR1, which presents a modified bacterial metabolite from the vitamin B2 biosynthesis pathway - this allows them to respond in the presence of many bacteria or yeast. MAIT cells also possess an array of cytokine receptors, which allows triggering independently of the TCR. The combination of such signals drives their functionality - this means they can respond to a range of stimuli and likely play a role not only in infection or inflammation, but also under homeostatic conditions.In this review, we will look at the question of what MAIT cells are doing in the normal liver and how they behave in the setting of disease. These questions are of relevance because MAIT cells are such a distinctive cell type enriched in the liver under normal conditions, and their modulation could be of therapeutic benefit. The recent discovery that they appear to be involved in liver fibrosis is particularly of interest in this context.
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Affiliation(s)
- Hema Mehta
- Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, South Parks Rd, Oxford, OX1 3SY, UK
| | - Martin Joseph Lett
- Liver Immunology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Paul Klenerman
- Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, South Parks Rd, Oxford, OX1 3SY, UK.
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
| | - Magdalena Filipowicz Sinnreich
- Liver Immunology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
- Department of Gastroenterology and Hepatology, Basel University Medical Clinic, Cantonal Hospital Baselland, Liestal, Switzerland
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Tourret M, Talvard-Balland N, Lambert M, Ben Youssef G, Chevalier MF, Bohineust A, Yvorra T, Morin F, Azarnoush S, Lantz O, Dalle JH, Caillat-Zucman S. Human MAIT cells are devoid of alloreactive potential: prompting their use as universal cells for adoptive immune therapy. J Immunother Cancer 2021; 9:jitc-2021-003123. [PMID: 34615705 PMCID: PMC8496386 DOI: 10.1136/jitc-2021-003123] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2021] [Indexed: 12/20/2022] Open
Abstract
Background Mucosal-associated invariant T (MAIT) cells are semi-invariant T cells that recognize microbial antigens presented by the highly conserved MR1 molecule. MAIT cells are predominantly localized in the liver and barrier tissues and are potent effectors of antimicrobial defense. MAIT cells are very few at birth and accumulate gradually over a period of about 6 years during the infancy. The cytotoxic potential of MAIT cells, as well as their newly described regulatory and tissue repair functions, open the possibility of exploiting their properties in adoptive therapy. A prerequisite for their use as ‘universal’ cells would be a lack of alloreactive potential, which remains to be demonstrated. Methods We used ex vivo, in vitro and in vivo models to determine if human MAIT cells contribute to allogeneic responses. Results We show that recovery of MAIT cells after allogeneic hematopoietic stem cell transplantation recapitulates their slow physiological expansion in early childhood, independent of recovery of non-MAIT T cells. In vitro, signals provided by allogeneic cells and cytokines do not induce sustained MAIT cell proliferation. In vivo, human MAIT cells do not expand nor accumulate in tissues in a model of T-cell-mediated xenogeneic graft-versus-host disease in immunodeficient mice. Conclusions Altogether, these results provide evidence that MAIT cells are devoid of alloreactive potential and pave the way for harnessing their translational potential in universal adoptive therapy overcoming barriers of HLA disparity. Trial registration number ClinicalTrials.gov number NCT02403089.
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Affiliation(s)
- Marie Tourret
- INSERM UMR976, Human Immunology, Pathophysiology and Immunotherapy, Université de Paris, Paris, France
| | - Nana Talvard-Balland
- INSERM UMR976, Human Immunology, Pathophysiology and Immunotherapy, Université de Paris, Paris, France
| | - Marion Lambert
- INSERM UMR976, Human Immunology, Pathophysiology and Immunotherapy, Université de Paris, Paris, France
| | - Ghada Ben Youssef
- INSERM UMR976, Human Immunology, Pathophysiology and Immunotherapy, Université de Paris, Paris, France
| | - Mathieu F Chevalier
- INSERM UMR976, Human Immunology, Pathophysiology and Immunotherapy, Université de Paris, Paris, France
| | - Armelle Bohineust
- INSERM UMR976, Human Immunology, Pathophysiology and Immunotherapy, Université de Paris, Paris, France
| | - Thomas Yvorra
- INSERM UMR3666/U1143, Université PSL, Institut Curie, Paris, France
| | - Florence Morin
- Laboratoire d'Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris, Paris, France
| | - Saba Azarnoush
- Département d'Immuno-Hématologie, Hôpital Robert Debré, AP-HP, Université de Paris, Paris, France
| | - Olivier Lantz
- INSERM U932, Université PSL, Institut Curie, Paris, France.,Laboratoire d'immunologie clinique & Centre d'investigation Clinique en Biothérapie (CIC-BT1428), Institut Curie, Paris, France
| | - Jean-Hugues Dalle
- INSERM UMR976, Human Immunology, Pathophysiology and Immunotherapy, Université de Paris, Paris, France.,Département d'Immuno-Hématologie, Hôpital Robert Debré, AP-HP, Université de Paris, Paris, France
| | - Sophie Caillat-Zucman
- INSERM UMR976, Human Immunology, Pathophysiology and Immunotherapy, Université de Paris, Paris, France .,Laboratoire d'Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris, Paris, France
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11
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Legoux F, Salou M, Lantz O. MAIT Cell Development and Functions: the Microbial Connection. Immunity 2021; 53:710-723. [PMID: 33053329 DOI: 10.1016/j.immuni.2020.09.009] [Citation(s) in RCA: 117] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/21/2020] [Accepted: 09/14/2020] [Indexed: 12/24/2022]
Abstract
Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved T cell subset, which reacts to most bacteria through T cell receptor (TCR)-mediated recognition of metabolites derived from the vitamin B2 biosynthetic pathway. Microbiota-derived signals affect all stages of MAIT cell biology including intra-thymic development, peripheral expansion, and functions in specific organs. In tissues, MAIT cells can integrate multiple signals and display effector functions involved in the defense against infectious pathogens. In addition to anti-bacterial activity, MAIT cells improve wound healing in the skin, suggesting a role in epithelium homeostasis through bi-directional interactions with the local microbiota. In humans, blood MAIT cell frequency is modified during several auto-immune diseases, which are often associated with microbiota dysbiosis, further emphasizing the potential interplay of MAIT cells with the microbiota. Here, we will review how microbes interact with MAIT cells, from initial intra-thymic development to tissue colonization and functions.
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Affiliation(s)
- François Legoux
- INSERM U932, PSL University, Institut Curie, Paris, 75005, France
| | - Marion Salou
- INSERM U932, PSL University, Institut Curie, Paris, 75005, France
| | - Olivier Lantz
- INSERM U932, PSL University, Institut Curie, Paris, 75005, France; Laboratoire d'immunologie clinique, Institut Curie, Paris, 75005, France; Centre d'investigation Clinique en Biothérapie, Institut Curie (CIC-BT1428), Paris, 75005, France.
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12
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Liu T, Wang J, Subedi K, Yi Q, Zhou L, Mi QS. MicroRNA-155 Regulates MAIT1 and MAIT17 Cell Differentiation. Front Cell Dev Biol 2021; 9:670531. [PMID: 33898469 PMCID: PMC8063056 DOI: 10.3389/fcell.2021.670531] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 03/17/2021] [Indexed: 12/29/2022] Open
Abstract
Mucosal-associated invariant T (MAIT) cells are innate-like T cells that develop in the thymus through three maturation stages to acquire effector function and differentiate into MAIT1 (T-bet+) and MAIT17 (RORγt+) subsets. Upon activation, MAIT cells release IFN-γ and IL-17, which modulate a broad spectrum of diseases. Recent studies indicate defective MAIT cell development in microRNA deficient mice, however, few individual miRNAs have been identified to regulate MAIT cells. MicroRNA-155 (miR-155) is a key regulator of numerous cellular processes that affect some immune cell development, but its role in MAIT cell development remains unclear. To address whether miR-155 is required for MAIT cell development, we performed gain-of-function and loss-of-function studies. We first generated a CD4Cre.miR-155 knock-in mouse model, in which miR-155 is over-expressed in the T cell lineage. We found that overexpression of miR-155 significantly reduced numbers and frequencies of MAIT cells in all immune organs and lungs and blocked thymic MAIT cell maturation through downregulating PLZF expression. Strikingly, upregulated miR-155 promoted MAIT1 differentiation and blocked MAIT17 differentiation, and timely inducible expression of miR-155 functionally inhibited peripheral MAIT cells secreting IL-17. miR-155 overexpression also increased CD4–CD8+ subset and decreased CD4–CD8– subset of MAIT cells. We further analyzed MAIT cells in conventional miR-155 knockout mice and found that lack of miR-155 also promoted MAIT1 differentiation and blocked MAIT17 differentiation but without alteration of their overall frequency, maturation and function. Overall, our results indicate that adequate miR-155 expression is required for normal MAIT1 and MAIT17 cell development and function.
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Affiliation(s)
- Tingting Liu
- Department of Dermatology, Center for Cutaneous Biology and Immunology Research, Henry Ford Health System, Detroit, MI, United States.,Shandong Provincial Hospital for Skin Diseases, Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China.,Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, United States
| | - Jie Wang
- Department of Dermatology, Center for Cutaneous Biology and Immunology Research, Henry Ford Health System, Detroit, MI, United States.,Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, United States
| | - Kalpana Subedi
- Department of Dermatology, Center for Cutaneous Biology and Immunology Research, Henry Ford Health System, Detroit, MI, United States.,Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, United States
| | - Qijun Yi
- Department of Dermatology, Center for Cutaneous Biology and Immunology Research, Henry Ford Health System, Detroit, MI, United States.,Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, United States
| | - Li Zhou
- Department of Dermatology, Center for Cutaneous Biology and Immunology Research, Henry Ford Health System, Detroit, MI, United States.,Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, United States
| | - Qing-Sheng Mi
- Department of Dermatology, Center for Cutaneous Biology and Immunology Research, Henry Ford Health System, Detroit, MI, United States.,Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI, United States
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13
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MAIT cells, guardians of skin and mucosa? Mucosal Immunol 2021; 14:803-814. [PMID: 33753874 PMCID: PMC7983967 DOI: 10.1038/s41385-021-00391-w] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 02/10/2021] [Accepted: 02/12/2021] [Indexed: 02/06/2023]
Abstract
Mucosal Associated Invariant T (MAIT) cells are evolutionary conserved innate-like T cells able to recognize bacterial and fungal ligands derived from vitamin B biosynthesis. These cells are particularly present in liver and blood but also populate mucosal sites including skin, oral, intestinal, respiratory, and urogenital tracts that are in contact with the environment and microbiota of their host. Growing evidence suggests important involvement of MAIT cells in safeguarding the mucosa against external microbial threats. Simultaneously, mucosal MAIT cells have been implicated in immune and inflammatory pathologies affecting these organs. Here, we review the specificities of mucosal MAIT cells, their functions in the protection and maintenance of mucosal barriers, and their interactions with other mucosal cells.
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14
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Yvorra T, Steinmetz A, Retailleau P, Lantz O, Schmidt F. Synthesis, biological evaluation and molecular modelling of new potent clickable analogues of 5-OP-RU for their use as chemical probes for the study of MAIT cell biology. Eur J Med Chem 2020; 211:113066. [PMID: 33341648 DOI: 10.1016/j.ejmech.2020.113066] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/27/2020] [Accepted: 11/27/2020] [Indexed: 02/08/2023]
Abstract
MAIT cells are preset αβ T lymphocytes that recognize a series of microbial antigens exclusively derived from the riboflavin biosynthesis pathway, which is present in most bacteria. The most active known antigen is unstable 5-(2-oxopropylideneamino)-6-(d-ribitylamino)uracil (5-OP-RU) which is stabilized when bound and presented to MAIT cells by MHC-related protein 1 (MR1). Here we describe the chemical synthesis and biological evaluation of new chemical probes for the study of MAIT cell biology. The two probes were ethinyl functionalized analogues of 5-OP-RU able to react through CuAAC also called "click chemistry". The molecules up-regulated more MR1 than 5-OP-RU and they efficiently activated iVα19 Vβ8 TCR transgenic murine MAIT cells but not iVα19 TCRα transgenic MAIT cells indicating a surprisingly strong impact of the TRCβ chain. Moreover, the use of these molecules as chemical probes was validated in vitro by efficient and selective binding to MR1 revealed via fluorescence microscopy. This study was also complemented by molecular modelling investigation of the probes and the binary/ternary complexes they form with MR1 and the TCR. These new probes will be crucial to delineate the dynamics of 5-OP-RU at the cellular or whole organism level and to identify the cells presenting 5-OP-RU to MAIT cells in vivo.
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Affiliation(s)
- Thomas Yvorra
- Institut Curie, PSL University, CNRS UMR3666, INSERM U1143, Paris, 75005, France
| | - Anke Steinmetz
- Centre de Recherche et Développement Vitry-Alfortville, IDD/ISDD, Sanofi-Aventis R&D, Vitry-sur-Seine, 94400, France
| | - Pascal Retailleau
- Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 1 Avenue de La Terrasse, Gif-sur-Yvette, 91190, France
| | - Olivier Lantz
- Institut Curie, PSL University, INSERM U932, Paris, 75005, France; Institut Curie, Laboratoire D'immunologie Clinique, Paris, 75005, France; Centre D'investigation Clinique en Biothérapie, Institut Curie (CIC-BT1428), Paris, 75005, France
| | - Frédéric Schmidt
- Institut Curie, PSL University, CNRS UMR3666, INSERM U1143, Paris, 75005, France.
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15
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Corbett AJ, Awad W, Wang H, Chen Z. Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries. Front Immunol 2020; 11:1961. [PMID: 32973800 PMCID: PMC7482426 DOI: 10.3389/fimmu.2020.01961] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 07/21/2020] [Indexed: 12/16/2022] Open
Abstract
Mucosal-associated Invariant T (MAIT) cells recognize vitamin B-based antigens presented by the non-polymorphic MHC class I related-1 molecule (MR1). Both MAIT T cell receptors (TCR) and MR1 are highly conserved among mammals, suggesting an important, and conserved, immune function. For many years, the antigens they recognize were unknown. The discovery that MR1 presents vitamin B-based small molecule ligands resulted in a rapid expansion of research in this area, which has yielded information on the role of MAIT cells in immune protection, autoimmune disease and recently in homeostasis and cancer. More recently, we have begun to appreciate the diverse nature of the small molecule ligands that can bind MR1, with several less potent antigens and small molecule drugs that can bind MR1 being identified. Complementary structural information has revealed the complex nature of interactions defining antigen recognition. Additionally, we now view MAIT cells (defined here as MR1-riboflavin-Ag reactive, TRAV1-2+ cells) as one subset of a broader family of MR1-reactive T cells (MR1T cells). Despite these advances, we still lack a complete understanding of how MR1 ligands are generated, presented and recognized in vivo. The biological relevance of these MR1 ligands and the function of MR1T cells in infection and disease warrants further investigation with new tools and approaches.
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Affiliation(s)
- Alexandra J. Corbett
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
| | - Wael Awad
- Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
- ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia
| | - Huimeng Wang
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Zhenjun Chen
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
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Xue H, Li H, Ju LL, Han XD, Cheng TC, Luo X, Chen L, Shao JG, She YJ, Bian ZL. Mucosal-associated invariant T cells in hepatitis B virus-related liver failure. World J Gastroenterol 2020; 26:4703-4717. [PMID: 32884227 PMCID: PMC7445862 DOI: 10.3748/wjg.v26.i31.4703] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 05/21/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver failure has high mortality and poor prognosis, and establishing new reliable markers for predicting its prognosis is necessary. Mucosal-associated invariant T (MAIT) cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease, and their potential role in liver failure remains unclear.
AIM To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus (HBV)-related liver failure.
METHODS We recruited 55 patients with HBV-related liver failure, 48 patients with chronic hepatitis B and 40 healthy controls (HCs) from Nantong Third People’s Hospital Affiliated to Nantong University. Peripheral blood mononuclear cells were isolated, and the percentage and number of circulating MAIT cells were detected by flow cytometry. Plasma levels of interleukin (IL)-7, IL-12p70, IL-18 and interferon-α were measured by Luminex assay.
RESULTS Circulating MAIT cells were significantly decreased in HBV-related liver failure patients (percentage: 2.00 ± 1.22 vs 5.19 ± 1.27%, P < 0.0001; number: 5.47 ± 4.93 vs 84.43 ± 19.59, P < 0.0001) compared with HCs. More importantly, there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure. Circulating MAIT cells partially recovered after disease improvement, both in percentage (4.01 ± 1.21 vs 2.04 ± 0.95%, P < 0.0001) and in cell count (17.24 ± 8.56 vs 7.41 ± 4.99, P < 0.0001). The proportion (2.29 ± 1.01 vs 1.58 ± 1.38%, P < 0.05) and number (7.30 ± 5.70 vs 2.94 ± 1.47, P < 0.001) of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group, and the Kaplan–Meier curve showed that lower expression of circulating MAIT cells (both percentage and cell count) predicted poor overall survival (P < 0.01). Also, the levels of IL-12 (20.26 ± 5.42 pg/mL vs 17.76 ± 2.79 pg/mL, P = 0.01) and IL-18 (1470.05 ± 1525.38 pg/mL vs 362.99 ± 109.64 pg/mL, P < 0.0001) were dramatically increased in HBV-related liver failure patients compared with HCs.
CONCLUSION Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker.
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Affiliation(s)
- Hong Xue
- Department of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Han Li
- Medical School of Nantong University, Nantong 226006, Jiangsu Province, China
| | - Lin-Ling Ju
- Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Xu-Dong Han
- Department of Critical Care Medicine, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Tiao-Chun Cheng
- Medical School of Nantong University, Nantong 226006, Jiangsu Province, China
| | - Xi Luo
- Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Lin Chen
- Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Jian-Guo Shao
- Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
- Department of Gastroenterology and Hepatology, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Yong-Jun She
- Department of Anesthesiology, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
| | - Zhao-Lian Bian
- Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
- Department of Gastroenterology and Hepatology, Nantong Third People’s Hospital, Nantong University, Nantong 226006, Jiangsu Province, China
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