IL-33 promotes serotonin release from enterochromaffin cells

胃肠道被认为是最大的内分泌器官，由于不断的环境挑战，它会遇到并整合各种免疫刺激和神经元反应。肠嗜铬（EC）细胞作为肠道上皮细胞上的化学传感器，已知其将环境信号转化为5-羟色胺（5-HT）的产生，从而促进肠道生理学。然而，免疫信号如何参与肠道感觉和神经内分泌反应仍不清楚。白细胞介素-33（IL-33）是一种通过警告系统潜在的环境应激而产生警报的细胞因子。我们在这里表明，IL-33诱导瞬时蠕动运动，促进鞭虫驱逐。我们发现IL-33可被EC细胞感受，诱导5-HT的释放。IL-33介导的5-HT释放激活肠神经元，随后促进肠道运动。从机制上讲，IL-33通过非经典信号通路特异性地在EC细胞中触发钙内流以诱导5-HT分泌。我们的数据建立了一个免疫神经内分泌轴校准快速释放5-HT肠内稳态。

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) is 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.