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

Immunity
Zuojia ChenChuan Wu

Abstract

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.

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Citations

Jan 14, 2021·Immunity·Lewis W Yu, Elaine Y Hsiao
Jun 4, 2021·Parasitology·Kelly S Hayes, Richard K Grencis
Aug 28, 2021·International Journal of Molecular Sciences·Claudia GüntherBeate Winner
Sep 3, 2021·Mucosal Immunology·Haozhe WangJoel C Bornstein
Sep 3, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sabah HaqWaliul I Khan

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