Interleukin-33 Promotes Serotonin Release from Enterochromaffin Cells for Intestinal Homeostasis. 2021

Zuojia Chen, and Jialie Luo, and Jian Li, and Girak Kim, and Andy Stewart, and Joseph F Urban, and Yuefeng Huang, and Shan Chen, and Ling-Gang Wu, and Alexander Chesler, and Giorgio Trinchieri, and Wei Li, and Chuan Wu
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.

The gastrointestinal tract is known as the largest endocrine organ that encounters and integrates various immune stimulations and neuronal responses due to constant environmental challenges. Enterochromaffin (EC) cells, which function as chemosensors on the gut epithelium, are known to translate environmental cues into serotonin (5-HT) production, contributing to intestinal physiology. However, how immune signals participate in gut sensation and neuroendocrine response remains unclear. Interleukin-33 (IL-33) acts as an alarmin cytokine by alerting the system of potential environmental stresses. We here demonstrate that IL-33 induced instantaneous peristaltic movement and facilitated Trichuris muris expulsion. We found that IL-33 could be sensed by EC cells, inducing release of 5-HT. IL-33-mediated 5-HT release activated enteric neurons, subsequently promoting gut motility. Mechanistically, IL-33 triggered calcium influx via a non-canonical signaling pathway specifically in EC cells to induce 5-HT secretion. Our data establish an immune-neuroendocrine axis in calibrating rapid 5-HT release for intestinal homeostasis.

UI MeSH Term Description Entries
D007422 Intestines The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE. Intestine
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010528 Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Peristalses
D004759 Enterochromaffin Cells A subtype of enteroendocrine cells found in the gastrointestinal MUCOSA, particularly in the glands of PYLORIC ANTRUM; DUODENUM; and ILEUM. These cells secrete mainly SEROTONIN and some neuropeptides. Their secretory granules stain readily with silver (argentaffin stain). Argentaffin Cells,5-HT-Containing Enterochromaffin Cells,Serotonin-Containing Enterochromaffin Cells,5 HT Containing Enterochromaffin Cells,5-HT-Containing Enterochromaffin Cell,Argentaffin Cell,Cell, Enterochromaffin,Cells, Enterochromaffin,Enterochromaffin Cell,Enterochromaffin Cell, 5-HT-Containing,Enterochromaffin Cell, Serotonin-Containing,Enterochromaffin Cells, 5-HT-Containing,Enterochromaffin Cells, Serotonin-Containing,Serotonin Containing Enterochromaffin Cells,Serotonin-Containing Enterochromaffin Cell
D006706 Homeostasis The processes whereby the internal environment of an organism tends to remain balanced and stable. Autoregulation
D000067596 Interleukin-33 A member of the INTERLEUKIN-1 protein family involved in the maturation of TH2 CELLS and the activation of MAST CELLS; BASOPHILS; EOSINOPHILS and NK CELLS. It is also produced by ENDOTHELIAL CELLS; EPITHELIAL CELLS and FIBROBLASTS; where it can function as an alarmin to modulate immune and inflammatory responses to tissue damage. IL-33,IL33,Interleukin 33
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D014257 Trichuriasis Infection with nematodes of the genus TRICHURIS, formerly called Trichocephalus. Trichocephaliasis,Trichuris Infection,Trichuris trichiura Infection,Whipworm Infection,Infection, Trichuris,Infection, Trichuris trichiura,Infection, Whipworm,Infections, Trichuris,Infections, Trichuris trichiura,Infections, Whipworm,Trichocephaliases,Trichuriases,Trichuris Infections,Trichuris trichiura Infections,Whipworm Infections

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