Schnell Julia T, Briviesca Raquel Laza, Kim Taehyeung, Charbonnier Louis-Marie, Henderson Lauren A, van Wijk Femke, Nigrovic Peter A
Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.
Department of Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.
Nat Rev Rheumatol. 2025 Jan;21(1):9-21. doi: 10.1038/s41584-024-01190-w. Epub 2024 Dec 9.
Classic regulatory T (T) cells expressing CD4 and the hallmark transcription factor FOXP3 are integral to the prevention of multi-system autoimmunity. However, immune-mediated arthritis is often associated with increased numbers of T cells in the inflamed joints. To understand these seemingly conflicting observations, which we collectively describe as 'the T paradox', we provide an overview of T cell biology with a focus on T cell heterogeneity, function and dysfunction in arthritis. We discuss how the inflamed environment constrains the immunosuppressive activity of T cells while also promoting the differentiation of T17-like T cell, exT cell (effector T cells that were formerly T cells), and osteoclastogenic T cell subsets that mediate tissue injury. We present a new framework to understand T cells in joint inflammation and define potential strategies for T cell-directed interventions in human inflammatory arthritis.
表达CD4和标志性转录因子FOXP3的经典调节性T（Treg）细胞对于预防多系统自身免疫至关重要。然而，免疫介导的关节炎通常与炎症关节中Treg细胞数量增加有关。为了理解这些看似相互矛盾的观察结果，我们将其统称为“Treg悖论”，本文将概述Treg细胞生物学，重点关注关节炎中Treg细胞的异质性、功能和功能障碍。我们将讨论炎症环境如何限制Treg细胞的免疫抑制活性，同时促进介导组织损伤的T17样T细胞、exTreg细胞（以前是Treg细胞的效应T细胞）和破骨细胞生成性Treg细胞亚群的分化。我们提出了一个新的框架来理解关节炎症中的Treg细胞，并确定针对人类炎症性关节炎中Treg细胞定向干预的潜在策略。
