美国国立癌症研究所Chuan Wu课题组发现，脂类通过肠道CD1d调节外周血清素释放。该项研究成果于2023年6月23日在线发表在《免疫》杂志上。

研究人员表明，脂质介导的恒定自然杀伤性T（iNKT）细胞与肠上皮细胞的一个亚群——肠嗜铬细胞（EC）细胞的接触，通过CD1d依赖的方式促进外周血清素（5-HT）释放，调节肠道运动和止血。研究人员还证明，来自共生微生物Bacteroides fragilis的抑制性鞘脂会抑制5-HT的释放。从机制上讲，CD1d结合在EC细胞上转发信号，并通过激活蛋白酪氨酸激酶Pyk2抑制钾的传导，导致钙的流入和5-HT的分泌。总之，这些数据显示，通过与iNKT细胞的接触，肠道化学感知细胞通过CD1d选择性地感知脂质抗原，以控制5-HT的释放，并调节肠道和系统的平衡状态。

据介绍，免疫和神经内分泌系统之间的交流对于肠道平衡和肠道-大脑的沟通至关重要。然而，目前仍不清楚免疫细胞如何参与肠道对激素和神经递质释放的感觉，以应对环境线索，如自我脂质和微生物脂质。

附：英文原文

Title: Lipids regulate peripheral serotonin release via gut CD1d

Author: Jialie Luo, Zuojia Chen, David Castellano, Bin Bao, Wenyan Han, Jian Li, Girak Kim, Dingding An, Wei Lu, Chuan Wu

Issue&Volume: 2023-06-23

Abstract: The crosstalk between the immune and neuroendocrine systems is critical for intestinalhomeostasis and gut-brain communications. However, it remains unclear how immune cellsparticipate in gut sensation of hormones and neurotransmitters release in responseto environmental cues, such as self-lipids and microbial lipids. We show here thatlipid-mediated engagement of invariant natural killer T (iNKT) cells with enterochromaffin(EC) cells, a subset of intestinal epithelial cells, promoted peripheral serotonin(5-HT) release via a CD1d-dependent manner, regulating gut motility and hemostasis.We also demonstrated that inhibitory sphingolipids from symbiotic microbe Bacteroides fragilis represses 5-HT release. Mechanistically, CD1d ligation on EC cells transduced a signaland restrained potassium conductance through activation of protein tyrosine kinasePyk2, leading to calcium influx and 5-HT secretion. Together, our data reveal thatby engaging with iNKT cells, gut chemosensory cells selectively perceive lipid antigensvia CD1d to control 5-HT release, modulating intestinal and systemic homeostasis.

DOI: 10.1016/j.immuni.2023.06.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00236-4