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，它遇到并整合了各种免疫刺激和神经元反应。肠嗜铬细胞(EC)在肠道上皮起化学感受器的作用，它能将环境信号转化为5-羟色胺(5-HT)的产生，从而促进肠道生理。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。白介素33(IL-33)是一种警示细胞因子，通过提醒系统潜在的环境压力。我们在这里证明了IL-33诱导瞬时蠕动和促进鞭虫排出。我们发现，IL-33可以被EC细胞感受到，诱导5-羟色胺的释放。IL-33介导的5-羟色胺释放激活肠神经元，进而促进肠运动。在机制上，IL-33通过一条非规范的信号通路，在EC细胞中特异性地触发钙内流，诱导5-羟色胺的分泌。我们的数据建立了一个免疫-神经内分泌轴，用于校准肠道内稳态的快速5-羟色胺释放。

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.