이길우 (전남대학교 의과대학, 화순전남대학교병원, 현 대웅제약)

한빛사논문

조회324

이길우Gil-Woo Lee

전남대학교 의과대학, 화순전남대학교병원, 현 대웅제약

Nat. Commun., 04 April 2024 | https://doi.org/10.1038/s41467-024-47144-4 Developmental self-reactivity determines pathogenic Tc17 differentiation potential of naive CD8+ T cells in murine models of inflammation

Gil-Woo Lee ^1,2,3, Young Ju Kim ^1,2,3,4, Sung-Woo Lee ^1,2,3, Hee-Ok Kim ⁵, Daeun Kim ⁵, Jiyoung Kim ⁶, You-Me Kim⁶, Keunsoo Kang ⁷, Joon Haeng Rhee ^1,2,4, Ik Joo Chung ^3,8, Woo Kyun Bae ^2,8, In-Jae Oh ⁸, Deok Hwan Yang ⁸ & Jae-Ho Cho ^1,2,3,4,*

¹Department of Microbiology and Immunology, Chonnam National University Medical School, Hwasun, Korea.
²Medical Research Center for Combinatorial Tumor Immunotherapy, Chonnam National University Medical School, Hwasun, Korea.
³Immunotherapy Innovation Center, Chonnam National University Medical School, Hwasun, Korea.
⁴BioMedical Sciences Graduate Program, Chonnam National University Medical School, Hwasun, Korea.
⁵Selecxine, Seoul, Korea.
⁶Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
⁷Department of Microbiology, College of Science & Technology, Dankook University, Cheonan, Korea.
⁸Department of Internal Medicine, Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.

^*Corresponding author: correspondence to Jae-Ho Cho

Abstract

The differentiation of naive CD8⁺ T cells into effector cells is important for establishing immunity. However, the effect of heterogeneous naive CD8⁺ T cell populations is not fully understood. Here, we demonstrate that steady-state naive CD8⁺ T cells are composed of functionally heterogeneous subpopulations that differ in their ability to differentiate into type 17 cytotoxic effector cells (Tc17) in a context of murine inflammatory disease models, such as inflammatory bowel disease and graft-versus-host disease. The differential ability of Tc17 differentiation is not related to T-cell receptor (TCR) diversity and antigen specificity but is inversely correlated with self-reactivity acquired during development. Mechanistically, this phenomenon is linked to differential levels of intrinsic TCR sensitivity and basal Suppressor of Mothers Against Decapentaplegic 3 (SMAD3) expression, generating a wide spectrum of Tc17 differentiation potential within naive CD8⁺ T cell populations. These findings suggest that developmental self-reactivity can determine the fate of naive CD8⁺ T cells to generate functionally distinct effector populations and achieve immense diversity and complexity in antigen-specific T-cell immune responses.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-05)
연구진국내 연구진
분야 생명과학 > 면역학

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