The thymus and rheumatology: should we care?
The thymus and rheumatology: should we care?
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DOI：
10.1097/bor.0000000000000251
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发表时间：
2016-03
影响因子：
5.1
通讯作者：
Prendergast C
中科院分区：
文献类型：
--
作者：
Cosway E;Anderson G;Garside P;Prendergast C
本综述的目的是讨论类风湿性关节炎 (RA) 中与 T 细胞介导的自身免疫相关的中枢和外周耐受机制。主要组织相容性复合体 II 类与 RA 之间已确立的关联使我们认识到 T 细胞和适应性免疫反应在疾病的发病机制中非常重要。为了发展自身免疫性疾病，对自身抗原的耐受性被破坏，中枢和外周耐受机制旨在防止这种情况发生。在这里，我们回顾了来自小鼠模型的证据，表明胸腺选择过程中 T 细胞受体信号阈值的变化可能与介导自身免疫性关节炎的 T 细胞逃逸有关。此外，我们总结了树突状细胞和 Foxp3+ 调节性 T 细胞在外周和胸腺耐受中的作用，并强调它们与我们所了解的 RA 病因学的相关性。胸腺中枢耐受机制和外周耐受机制可以控制自身反应性 T 细胞并预防自身免疫性疾病的发生。我们预计，对这些机制的更好理解将有助于开发出更好的抗原特异性疗法来恢复耐受性。
The purpose of this review is to discuss the mechanisms of central and peripheral tolerance in relation to T-cell mediated autoimmunity in rheumatoid arthritis (RA). The well established association between major histocompatibility complex class II and RA has led us to understand that T cells, and the adaptive immune response, are important in the pathogenesis of disease. In order for autoimmune disease to develop, there is a breach of tolerance to self antigen and the mechanisms of both central and peripheral tolerance aim to prevent this. Here, we review evidence from mouse models indicating that alterations in T-cell receptor signalling thresholds during thymic selection may be linked to the escape of T cells that mediate autoimmune arthritis. In addition, we summarize the role of dendritic cells and Foxp3+ regulatory T cells in both peripheral and thymic tolerance, and highlight their relevance to what we know about the aetiology of RA. Mechanisms of central tolerance in the thymus and peripheral tolerance are in place to control autoreactive T cells and to prevent the development of autoimmune disease. We anticipate that a better understanding of these mechanisms will lead to the development of better, antigen-specific therapeutics to restore tolerance.