美国哈佛大学Wendy S. Garrett团队近期的研究工作发现，代谢感知受体Ffar2参与调节结肠3型先天淋巴样细胞（ILC3）和肠道免疫。相关论文发表在2019年11月19日出版的《免疫》杂志上。

研究人员发现结肠ILC3表达Ffar2，一种微生物代谢物感应受体，并且Ffar2激动作用促进ILC3的扩增和功能。ILC3中Ffar2的缺乏会降低其原位增殖和ILC3来源的白介素22（IL-22）的产生。这导致肠上皮功能受损，其特征在于粘液相关蛋白和抗菌肽发生改变，并且对结肠损伤和细菌感染的敏感性增加。

Ffar2增加结肠淋巴组织中IL-22/CCR6双阳性ILC3的表达，并影响ILC3的丰度。Ffar2激动通过AKT和STAT3轴差异激活AKT或ERK信号，并增加ILC3来源的IL-22。这些研究结果表明Ffar2调节结肠ILC3增殖和功能，并且确定了ILC3受体调节肠道稳态和病原体防御的信号传导途径。

据介绍，ILC3感知对肠道稳态和宿主防御至关重要的环境信号。然而，调节结肠ILC3的代谢物感应G蛋白偶联受体仍然知之甚少。

附：英文原文

Title: Metabolite-Sensing Receptor Ffar2 Regulates Colonic Group 3 Innate Lymphoid Cells and Gut Immunity

Author: Eunyoung Chun, Sydney Lavoie, Diogo Fonseca-Pereira, Sena Bae, Monia Michaud, Hamid R. Hoveyda, Graeme L. Fraser, Carey Ann Gallini Comeau, Jonathan N. Glickman, Miles H. Fuller, Brian T. Layden, Wendy S. Garrett

Issue&Volume: 2019/11/19

Abstract: Group 3 innate lymphoid cells (ILC3s) sense environmental signals that are critical for gut homeostasis and host defense. However, the metabolite-sensing G-protein-coupled receptors that regulate colonic ILC3s remain poorly understood. We found that colonic ILC3s expressed Ffar2, a microbial metabolite-sensing receptor, and that Ffar2 agonism promoted ILC3 expansion and function. Deficiency of Ffar2 in ILC3s decreased their in situ proliferation and ILC3-derived interleukin-22 (IL-22) production. This led to impaired gut epithelial function characterized by altered mucus-associated proteins and antimicrobial peptides and increased susceptibility to colonic injury and bacterial infection. Ffar2 increased IL-22+ CCR6+ ILC3s and influenced ILC3 abundance in colonic lymphoid tissues. Ffar2 agonism differentially activated AKT or ERK signaling and increased ILC3-derived IL-22 via an AKT and STAT3 axis. Our findings suggest that Ffar2 regulates colonic ILC3 proliferation and function, and they identify an ILC3-receptor signaling pathway modulating gut homeostasis and pathogen defense.

DOI: 10.1016/j.immuni.2019.09.014

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30410-8