Bystander memory-phenotype conventional CD4 + T cells exacerbating autoimmune neuroinflammation
Bystander memory-phenotype conventional CD4 + T cells exacerbating autoimmune neuroinflammation
Abstract Memory-phenotype (MP) CD4+ T cells are a substantial population of conventional T cells that exist in steady-state mice, and their immunologic functions in autoimmune disease have not yet been studied. In this work, we unveil a unique phenotype of MP CD4+ T cells by analyzing single-cell transcriptomics and T cell receptor (TCR) repertoires. We found that steady-state MP CD4+ T cells exist regardless of germ and food-antigen which are composed of heterogenous effector subpopulations. Distinct subpopulations of MP CD4+ T cells are specifically activated by IL-1 family cytokines and STAT activators, revealing that the cells have TCR-independent effector functions. Especially, CCR6high MP CD4+ T cells are major responders to IL-1β and IL-23 without MOG35-55 antigen reactivity, which gives them pathogenic-Th17 characteristics and allows them to contribute to autoimmune encephalomyelitis. We identified Bhlhe40 in CCR6high MP CD4+ T cells drives the expression of GM-CSF, contributing to CNS pathology in experimental autoimmune encephalomyelitis. Collectively, our findings reveal heterogeneity of MP CD4+ T cells that can contribute to autoimmune neuroinflammation in bystander manner synergistically with antigen-specific T cells.
Yoon Jae-Won、Taneja Reshma、Choi Je-Min、Cho Min-Zi、Edelson Brian T.、Kim Gil-Ran、Koo Ja-Hyun、Lee You Jeong、Lee Hong-Gyun
Department of Life Science, College of Natural Sciences, Hanyang UniversityDepartment of Physiology and Healthy Longevity Translation Research Program, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Life Science, College of Natural Sciences, Hanyang University||Research Institute for Natural Sciences, Hanyang University||Research Institute for Convergence of Basic Sciences, Hanyang UniversityDepartment of Life Science, College of Natural Sciences, Hanyang UniversityDepartment of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of MedicineDepartment of Life Science, College of Natural Sciences, Hanyang UniversityDepartment of Life Science, College of Natural Sciences, Hanyang University||The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard UniversityResearch Institute of Pharmaceutical Sciences, Seoul National UniversityDepartment of Life Science, College of Natural Sciences, Hanyang University||Ann Romney Center for Neurologic Diseases, Brigham and Women?ˉs Hospital, Harvard Medical School
基础医学神经病学、精神病学分子生物学
Memory-phenotype CD4+ T cellsBystanderEAEAutoimmune neuroinflammationCCR6TCR independentBhlhe40
Yoon Jae-Won,Taneja Reshma,Choi Je-Min,Cho Min-Zi,Edelson Brian T.,Kim Gil-Ran,Koo Ja-Hyun,Lee You Jeong,Lee Hong-Gyun.Bystander memory-phenotype conventional CD4 + T cells exacerbating autoimmune neuroinflammation[EB/OL].(2025-03-28)[2025-06-27].https://www.biorxiv.org/content/10.1101/2022.06.17.496529.点此复制
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