M cell–dependent commensal uptake confers encephalitogenic phenotypes on γδT17 cells in Peyer’s patches
Abstract
Interleukin-17-producing γδT cells (γδT17 cells) play a dual role in immune regulation, serving as both protectors in various tissues and orchestrators of inflammatory responses in autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis. However, the ontology and repertoires of encephalitogenic γδT17 cells remain unclear. In this study, we demonstrate that the encephalitogenicity of γδT17 cells is conferred through microfold cell (M cell)-dependent uptake of commensal bacteria in Peyer’s patches. Specifically, CXCR6 hi Vγ6 + Vδ1 + invariant γδT17 cells are activated by specific commensal bacteria such as Lactobacillus spp., which stimulate TCR of CXCR6 hi Vγ6 + Vδ1 + invariant γδT17 cells. During the early stages of EAE, γδT17 cells infiltrate the central nervous system (CNS), initiating a type 17 inflammatory response. Our findings illustrate that Peyer’s patch M cells serve as a critical bridge, linking the pathological association between commensal bacteria and the onset of CNS inflammation.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (24)
Seiga Komiyama
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Yotaro Kodaira
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Rae Maeda
Multi-Omics Platform, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine
Yuki Sugiura
Koichiro Suzuki
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Aiko Saeki
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Yusuke Kinashi
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Hiroyuki Oguchi
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Kokona Takano
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Satoshi Onawa
Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology
Ako Matsui
Division of Allergy and Immunology, Medical Institute of Bioregulation, Kyushu University
Eita Sasaki
Division of Analytical Chemistry for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Kisara Hattori-Muroi
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Shunsuke Kimura
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Yumiko Fujimura
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Yuyo Ka
Humanized Model Laboratory, Animal Resource Technical Research Center, Central Institute for Experimental Medicine and Life Science
Tomoyuki Ogura
Humanized Model Laboratory, Animal Resource Technical Research Center, Central Institute for Experimental Medicine and Life Science
Kenjiro Hanaoka
Division of Analytical Chemistry for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University
Minako Ito
Hiroshi Watarai
Department of Immunology and Stem Cell Biology, Kanazawa University
Tsuneyasu Kaisho
Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University
Nobuyuki Udagawa
Department of Biochemistry, Matsumoto Dental University
Daisuke Takahashi
Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University
Koji Hase
Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University