Copyright
©The Author(s) 2021.
World J Gastrointest Pathophysiol. May 22, 2021; 12(3): 25-39
Published online May 22, 2021. doi: 10.4291/wjgp.v12.i3.25
Published online May 22, 2021. doi: 10.4291/wjgp.v12.i3.25
Neuromediator | Distribution | Binding receptor | Function |
SP | Neurons and inflammatory cells like lymphocytes, macrophages, and dendritic cells | NK-1R | Exerts pro-inflammatory effects in epithelial and immune cells and contributes to inflammatory diseases. In murine model of colitis, it plays regulatory role |
NT | Nervous system and intestine | NTR1 | Recognized as an immunomodulator. By interacting with immune cells, it enhances the chemotaxis and induces the cytokine release to modulate the immune response. In IBD, it exerts its pro-inflammatory effects by promoting the expression of miR-210 in intestinal epithelial cells |
NPY | Central and peripheral nervous system and immune cells | Out of five receptors of NPY, NPYY1 is known to play a crucial role in immunomodulation | Regulates various immune cell functions such as T helper cell differentiation, neutrophil chemotaxis, natural killer cell activity, and granulocyte oxidative burst and NO production. In the gut, NPY is known to exert pro-inflammatory effects |
VIP | Neuronal and lymphoid cells | VIPR1 and VIPR2 | Identified as an anti-inflammatory molecule. administration of VIP nanomedicine in the form of VIP-SSM are capable of alleviating the symptoms of DSS- induced mice model of colitis |
GAL | Vasculature, immune cells and colonic epithelial cells | GAL (1-3) receptor | Exerts anti-inflammatory effects in TNBS induced colitis model by reducing the expression and activity of iNOS |
CRH | Immune cells | CRH-R1 and CRH-R2 | It acts as a pro-inflammatory peptide. The expression pattern of CRH 1 and CRH 2 varies in ulcerative colitis. Inhibition of CRH1 and overexpression of CRH2 may have the therapeutic potential in IBD |
CGRP | Sensory nerves projecting to the lymphoid organs, airways, and pulmonary neuroendocrine cells | CGRP receptors | CGRP negatively regulates innate immune responses and thus has potential anti-inflammatory effects. Its expression reduced in the colon of an animal model of colitis |
NA | Nerves innervating the peripheral lymphoid organs | Adrenergic α and β receptors | immunomodulatory effect of NA is administered via cAMP. Activation of NA receptors that stimulate cAMP resulting in a shift toward Th2 responses which are anti-inflammatory and neuroprotective whereas decreased cAMP stimulates Th1 responses resulting in cell destruction and inflammation |
Acetylcholine | Central and peripheral nervous system, immune cells, keratinocytes, endothelial cells, urothelial cells of the urinary bladder, airways and epithelial cells of the placenta | Nicotinic and muscarinic receptors | Muscarinic receptors mediate pro-inflammatory responses and nicotinic receptors enhance anti-inflammatory responses. Treatment of UC via nicotine suggests the role of the cholinergic pathway in colonic inflammation |
NO | Neuron synapses and immune cells | NO does not act via receptors. its specificity for target cell depends on its concentration, its activity and response, and territory of target cells | NO is oxidised to reactive nitrogen oxide species which mediate most of the immunological effects. It regulates the growth, functional activity, and death of immune cells. It acts as a biomarker for monitoring disease activity due to its increased serum concentration during the active phase of both UC and CD and reduced concentration during the inactive phase of the disease |
Serotonin or 5-HT | Central nervous system and EC cells of GIT | 5-HT receptor | It promotes activation of lymphocytes and secretion of pro-inflammatory cytokines. It activates the signalling molecules of the NF-kB pathway during gut inflammation |
GABA | Nervous system and immune system | GABA- AR and GABA-BR | GABA has several effects on immune cells, including modulation of cytokine secretion, regulation of cell proliferation, and migration. Activation of GABA-A receptor aggravates DSS induced mice model of colitis |
- Citation: Aggarwal S, Ranjha R, Paul J. Neuroimmunomodulation by gut bacteria: Focus on inflammatory bowel diseases. World J Gastrointest Pathophysiol 2021; 12(3): 25-39
- URL: https://www.wjgnet.com/2150-5330/full/v12/i3/25.htm
- DOI: https://dx.doi.org/10.4291/wjgp.v12.i3.25