Cell . . . The intestinal nervous system participates in the mucous membrane immune barrier by secreting IL18.

The enteric nervous system (ENS) is located in every corner of the intestinal tissue, which can quickly transmit the collected information to other types of cells or intestinal resident microorganisms, forming a large and complex network system [1].a number of recent studies have found that ENS can be used as a sensing platform of the immune system [2].previous studies have deeply analyzed the important role of the interaction between epithelial cells and immune system in maintaining intestinal homeostasis in intestinal tissues, but how ens and epithelial cells interact, what are the mediators, and what is the mode of action are still unknown.on January 9, 2020, Richard A. Flavell and ruaidhr í Jackson of Yale University School of medicine and roni nowarski of Harvard Medical School published an article entitled "enterprise nervous system derived IL-18 orchestrates mucosal barrier immunity" in cell.studies have found that ENS neurons secrete IL-18, which acts on goblet cells in intestinal epithelial cells, promotes the expression of antimicrobial protein AMP in goblet cells and maintains intestinal homeostasis.IL-18 is a proinflammatory cytokine, which plays an important role in anti-invasive bacterial infection.epithelial cells express IL-18 at steady state, while myeloid cells rapidly up regulate IL-18 expression when inflammation occurs.however, the authors found that the specific knockout of IL-18 in immune cells or epithelial cells did not affect the body's resistance to Salmonella typhimurium (S.T.), and the role of IL-18 from the two cell sources was compensated by other molecules in the inflammatory state.however, epithelial IL-18 plays an important role in maintaining intestinal homeostasis in resting state.after that, the author turned to ens derived cytokines.after a series of staining, it was found that the ENS in colon tissue could also express IL-18, and most of the neurons expressing IL-18 were located near the epithelial cells.the authors analyzed two open single cell transcriptome data sets and found that all types of neurons in ENS can express IL-18, but the expression abundance of IL-1 β is much lower than that of IL-18.next, the authors used a variety of tool mice to construct the ENS specific IL-18 knockout mice (il18f / F nestert +, il1f / fplp1 + intestinal glial cell specific; il18f / fhand2 +, Hand2 is an essential transcription factor for ENS differentiation) and a variety of cell type specific IL-18R knockout mice (il18r1f / F nesert +, il18r1f / fplp1 +, il18r1f / fhand2 +), il18r1f / fhand2 +, il18r1f / fhand2 +, il18r1f / fhand2 +, respectively; Il18r1f / fflk1 + is specific for hematopoietic stem cells and endothelial cells; il18r1f / fvil1 + is combined with single cell transcriptome technology to explore the function and mode of action of ENS derived IL-18.finally, it was found that the expression of AMP in colonic goblet cells was induced by IL-18, which could resist bacterial invasion. Moreover, IL-18 did not affect the differentiation of goblet cells, promote intestinal peristalsis and produce catecholamine, but specifically promoted the expression of AMP and inhibited bacterial invasion and infection.in the past five years, the research on how ENS regulates intestinal tissue has increased rapidly.more and more studies have focused on the interaction of other cell types in the nervous system and intestinal tissue.this study revealed for the first time that ENS can produce IL-18, a specific group of IL-18, which drives colonic goblet cells to secrete amp and resist bacterial invasion. In this paper, the author's reference 1. Matheis, F., Muller, P.A., graves, C.L., gabanyi, I., Kerner, z.j., Costa Borges, D., and mucida, D. (2019). Adrergic signaling in muscularis macrophases limits limits neural death following enterinfiection. Biorxiv. Lai, N.Y., Musser, M.A., Pinho Ribeiro, F.A. a, F.A., M.A., Pinho Ribeiro, F.A. a, F.A, M.A., Pinho Ribeiro, F.A. a, F.A., M.A., Pinho Ribeiro, F.A., F.A., N.Y., Musser, M.A., M.A., Pinho Ribeiro, F.A, F.A., F.A.,, Baral, P., Ma, P, Potts, D.E., Chen, Z., Paik, D., Soualhi, S., Shi, H., et al. (2019). Gut-innervating nociceptor neurons protect against enteric infection by modulating the microbiota and Peyer’s patch microfold cells. bioRxiv.  Nowarski, R., Jackson, R., Gagliani, N., de Zoete, M.R., Palm, N.W., Bailis, W., Low, J.S., Harman, C.C., Graham, M., Elinav, E., and Flavell, R.A. (2015). Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis. Cell 163, 1444–1456.