4.8 Article

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

Journal

IMMUNITY
Volume 54, Issue 1, Pages 151-+

Publisher

CELL PRESS
DOI: 10.1016/j.immuni.2020.10.014

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Funding

  1. National Multiple Sclerosis Society Career Transition Award [TA 3059-A-2]

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The study demonstrates that interleukin-33 (IL-33) can induce serotonin (5-HT) release by activating enterochromaffin (EC) cells, subsequently regulating gut motility and maintaining intestinal homeostasis.
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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