한빛사논문
- 조회643
Min-Ji Cho1,10, Hong-Gyun Lee1,2,10, Jae-Won Yoon1, Gil-Ran Kim1, Ja-Hyun Koo1,3, Reshma Taneja4, Brian T. Edelson5, You Jeong Lee6 and Je-Min Choi1,7,8,9
1Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea.
2Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
3The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
4Department of Physiology and Healthy Longevity Translation Research Program, Yong Loo Lin School of Medicine, National University of Singapore, 117593 Singapore, Singapore.
5Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO 63119, USA.
6Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
7Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea.
8Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul 04763, Republic of Korea.
9Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul 04763, Korea.
10These authors contributed equally: Min-Ji Cho, Hong-Gyun Lee.
Corresponding author : Correspondence to Je-Min Choi.
Abstract
Memory-phenotype (MP) CD4+ T cells are a substantial population of conventional T cells that exist in steady-state mice, yet their immunological roles in autoimmune disease remain unclear. In this work, we unveil a unique phenotype of MP CD4+ T cells determined by analyzing single-cell transcriptomic data and T cell receptor (TCR) repertoires. We found that steady-state MP CD4+ T cells in the spleen were composed of heterogeneous effector subpopulations and existed regardless of germ and food antigen exposure. Distinct subpopulations of MP CD4+ T cells were specifically activated by IL-1 family cytokines and STAT activators, revealing that the cells exerted TCR-independent bystander effector functions similar to innate lymphoid cells. In particular, CCR6high subpopulation of MP CD4+ T cells were major responders to IL-23 and IL-1β without MOG35-55 antigen reactivity, which gave them pathogenic Th17 characteristics and allowed them to contribute to autoimmune encephalomyelitis. We identified that Bhlhe40 in CCR6high MP CD4+ T cells as a key regulator of GM-CSF expression through IL-23 and IL-1β signaling, contributing to central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis. Collectively, our findings reveal the clearly distinct effector-like heterogeneity of MP CD4+ T cells in the steady state and indicate that CCR6high MP CD4+ T cells exacerbate autoimmune neuroinflammation via the Bhlhe40/GM-CSF axis in a bystander manner.
논문정보
- Research article
- 2023년 05월 (BRIC 등록일 2023-05-17)
- 국내(교신)+국외 연구진
- 생명과학 > 면역학
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