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.

胃肠道被称为最大的内分泌器官，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。肠嗜铬细胞 (EC) 细胞作为肠道上皮细胞的化学传感器，已知可将环境信号转化为血清素 (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。白细胞介素 33 (IL-33) 通过提醒系统潜在的环境压力而充当警报素细胞因子。我们在这里证明 IL-33 诱导瞬时蠕动运动并促进Trichuris muris开除。我们发现 EC 细胞可以感知 IL-33，从而诱导 5-HT 的释放。IL-33 介导的 5-HT 释放激活的肠神经元，随后促进肠道运动。从机制上讲，IL-33 通过特异性在 EC 细胞中的非典型信号通路触发钙内流，从而诱导 5-HT 分泌。我们的数据建立了一个免疫神经内分泌轴，用于校准肠道稳态的快速 5-HT 释放。