IL-33 promotes serotonin release from enterochromaffin cells

胃肠道被认为是最大的内分泌器官， 整合了各种免疫刺激和神经元反应，由于不断的环境 挑战肠嗜铬（EC）细胞作为肠道上皮细胞上的化学传感器 已知将环境线索转化为5-羟色胺（5-HT）的产生，有助于 肠道生理学然而，免疫信号如何参与肠道感觉， 神经内分泌反应尚不清楚。白细胞介素-33（IL-33）是一种警报细胞因子， 警告系统潜在的环境压力。我们在此证明IL-33 诱导瞬时蠕动运动，并促进鞭虫排出。我们发现 EC细胞能感受到IL-33，诱导5-HT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。机械上，IL-33 通过EC细胞中特异性的非经典信号通路触发钙内流， 诱导5-HT分泌。我们的数据建立了一个免疫-神经内分泌轴， 5-HT释放用于肠内稳态。

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.