Exploring the role of unconventional T cells in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by sustained synovial inflammation and the gradual destruction of joint structures. Although conventional T cells have historically been viewed as central to RA pathogenesis, increasing attention has recently focused on unconve...

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Main Authors: Tangqing Xu, Hao Cai, Jianye Liu, Xingxing Mao, Yulong Chen, Minhao Chen, Youhua Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1656994/full
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author Tangqing Xu
Hao Cai
Jianye Liu
Xingxing Mao
Yulong Chen
Minhao Chen
Youhua Wang
author_facet Tangqing Xu
Hao Cai
Jianye Liu
Xingxing Mao
Yulong Chen
Minhao Chen
Youhua Wang
author_sort Tangqing Xu
collection DOAJ
description Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by sustained synovial inflammation and the gradual destruction of joint structures. Although conventional T cells have historically been viewed as central to RA pathogenesis, increasing attention has recently focused on unconventional T cell subsets, such as natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and gamma delta T (γδ T) cells. Functioning as a bridge between innate and adaptive immunity, these cells contribute to RA immunopathogenesis by producing cytokines, exerting cytotoxic effects, and interacting with various immune and stromal cells. This review offers a comprehensive analysis of the immunological characteristics and pathogenic roles of unconventional T cell subsets in RA. NKT, MAIT, and γδ T cells contribute to the amplification of inflammatory responses and joint tissue destruction through diverse mechanisms, exhibiting unique tissue tropism and functional plasticity. Recently, novel therapeutic strategies have been developed to target these subsets, including modulation of antigen presentation pathways, inhibition of pro-inflammatory signaling cascades, and reprogramming of cellular functionalities. Advancements in single-cell omics and spatial immune profiling have facilitated the precise identification and characterization of pathogenic unconventional T cell subsets in the RA synovium, thereby paving the way for personalized immunotherapeutic approaches.
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institution Kabale University
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publishDate 2025-08-01
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series Frontiers in Immunology
spelling doaj-art-47a39ecb1dca41338a77c5ab9a9b1cb82025-08-20T05:33:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16569941656994Exploring the role of unconventional T cells in rheumatoid arthritisTangqing XuHao CaiJianye LiuXingxing MaoYulong ChenMinhao ChenYouhua WangRheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by sustained synovial inflammation and the gradual destruction of joint structures. Although conventional T cells have historically been viewed as central to RA pathogenesis, increasing attention has recently focused on unconventional T cell subsets, such as natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and gamma delta T (γδ T) cells. Functioning as a bridge between innate and adaptive immunity, these cells contribute to RA immunopathogenesis by producing cytokines, exerting cytotoxic effects, and interacting with various immune and stromal cells. This review offers a comprehensive analysis of the immunological characteristics and pathogenic roles of unconventional T cell subsets in RA. NKT, MAIT, and γδ T cells contribute to the amplification of inflammatory responses and joint tissue destruction through diverse mechanisms, exhibiting unique tissue tropism and functional plasticity. Recently, novel therapeutic strategies have been developed to target these subsets, including modulation of antigen presentation pathways, inhibition of pro-inflammatory signaling cascades, and reprogramming of cellular functionalities. Advancements in single-cell omics and spatial immune profiling have facilitated the precise identification and characterization of pathogenic unconventional T cell subsets in the RA synovium, thereby paving the way for personalized immunotherapeutic approaches.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1656994/fullunconventional T cellsnatural killer T (NKT) cellsmucosal-associated invariant T (MAIT) cellsgamma delta T (γδ T) cellsrheumatoid arthritis (RA)
spellingShingle Tangqing Xu
Hao Cai
Jianye Liu
Xingxing Mao
Yulong Chen
Minhao Chen
Youhua Wang
Exploring the role of unconventional T cells in rheumatoid arthritis
Frontiers in Immunology
unconventional T cells
natural killer T (NKT) cells
mucosal-associated invariant T (MAIT) cells
gamma delta T (γδ T) cells
rheumatoid arthritis (RA)
title Exploring the role of unconventional T cells in rheumatoid arthritis
title_full Exploring the role of unconventional T cells in rheumatoid arthritis
title_fullStr Exploring the role of unconventional T cells in rheumatoid arthritis
title_full_unstemmed Exploring the role of unconventional T cells in rheumatoid arthritis
title_short Exploring the role of unconventional T cells in rheumatoid arthritis
title_sort exploring the role of unconventional t cells in rheumatoid arthritis
topic unconventional T cells
natural killer T (NKT) cells
mucosal-associated invariant T (MAIT) cells
gamma delta T (γδ T) cells
rheumatoid arthritis (RA)
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1656994/full
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