Unknown

Dataset Information

0

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


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.

SUBMITTER: Chun E 

PROVIDER: S-EPMC6901086 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications


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  ...[more]

Similar Datasets

2019-09-16 | GSE137508 | GEO
| S-EPMC3268875 | biostudies-literature
| S-EPMC8062677 | biostudies-literature
| S-EPMC4925019 | biostudies-literature
| S-EPMC6539149 | biostudies-literature
| S-EPMC6626542 | biostudies-literature
| S-EPMC3035987 | biostudies-literature
| S-EPMC5772175 | biostudies-literature
| S-EPMC7524156 | biostudies-literature
| S-EPMC5461001 | biostudies-literature