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

Authors
  • Chun, Eunyoung1
  • Lavoie, Sydney1
  • Fonseca-Pereira, Diogo1
  • Bae, Sena1
  • Michaud, Monia1
  • Hoveyda, Hamid R2
  • Fraser, Graeme L3
  • Gallini Comeau, Carey Ann1
  • Glickman, Jonathan N4
  • Fuller, Miles H5
  • Layden, Brian T6
  • Garrett, Wendy S7
  • 1 Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
  • 2 Euroscreen SA, 6041 Gosselies, Belgium. , (Belgium)
  • 3 EPICS SA, 6041 Gosselies, Belgium. , (Belgium)
  • 4 Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. , (Israel)
  • 5 Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 6 Division of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, Chicago, IL 60612, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA.
  • 7 Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: [email protected]
Type
Published Article
Journal
Immunity
Publication Date
Nov 19, 2019
Volume
51
Issue
5
Identifiers
DOI: 10.1016/j.immuni.2019.09.014
PMID: 31628054
Source
Medline
Keywords
Language
English
License
Unknown

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. Copyright © 2019 Elsevier Inc. All rights reserved.

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