전은영 (Harvard T.H. Chan School of Public Health)

한빛사논문

조회2,337

Harvard T.H. Chan School of Public Health

CV File 164 kb

Immunity, Volume 51, Issue 5, 19 November 2019, Pages 871-884.e6 | https://doi.org/10.1016/j.immuni.2019.09.014 Metabolite-Sensing Receptor Ffar2 Regulates Colonic Group 3 Innate Lymphoid Cells and Gut Immunity

Eunyoung Chun¹, Sydney Lavoie¹, Diogo Fonseca-Pereira¹, Sena Bae¹, Monia Michaud¹, Hamid R. Hoveyda², Graeme L. Fraser³, Carey Ann Gallini Comeau¹, Jonathan N. Glickman^4,5, Miles H. Fuller⁶, Brian T. Layden^7,8, Wendy S. Garrett^1,9,10,11,*

¹Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
²Euroscreen SA, 6041 Gosselies, Belgium
³EPICS SA, 6041 Gosselies, Belgium
⁴Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
⁵Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
⁶Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
⁷Division of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, Chicago, IL 60612, USA
⁸Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA
⁹Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
¹⁰Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
¹¹Lead Contact

^*Corresponding author

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.

논문정보

형식Research article
게재일2019년 11월 (BRIC 등록일 2019-11-28)
연구진국외 연구진
분야

댓글 작성 로그인

CV 열람하기

연락처 보기