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系统性硬化症中的 T 细胞异常。

T cell abnormalities in systemic sclerosis.

机构信息

Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China.

Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China; National Translational Science Center for Molecular Medicine, Xi'an, PR China.

出版信息

Autoimmun Rev. 2022 Nov;21(11):103185. doi: 10.1016/j.autrev.2022.103185. Epub 2022 Aug 27.

Abstract

Systemic sclerosis (SSc) is an autoimmune disease with a poor prognosis. To date, the pathogenesis of SSc is still unclear; moreover, its pathological conditions include microvascular damage, inflammation, and immune abnormalities. Different types of T cells may cause vasculitis and fibrosis in SSc by means of up- and down-regulation of cell surface molecules, abnormal release of pro-fibrotic or pro-inflammatory cytokines and direct contact with fibroblasts. These T cells, which are mainly CD4 + T cells, include the subtypes, T follicular helper (Tfh) cells, regulatory T Cells (Treg), interleukin-17 (IL-17)-producing Th17 cells, CD4 cytotoxic T lymphocytes (CTLs), and angiogenic T (Tang) cells. In addition to the Th1/Th2 imbalance, which has long been established, there is also a Th17/Treg imbalance in SSc. This imbalance may be closely related to the abnormal immune status of SSc. There is mounting evidence that suggest T cell abnormalities may be crucial to the pathogenesis of SSc. In terms of treatment, existing therapies that target T cells, such as immunosuppressive therapy (tacrolimus), Janus kinase(JAK) inhibitors, and biologics(abatacept), have had some success. Other non-drug therapies, including Mesenchymal stem cells (MSCs), have extensive and complex mechanisms of action actually including T cell regulation. Based on the current evidence, we believe that the study of T cells will further our understanding of the pathogenesis of SSc, and may lead to more targeted treatment optionsfor patients with SSc.

摘要

系统性硬化症(SSc)是一种预后不良的自身免疫性疾病。迄今为止,SSc 的发病机制仍不清楚;此外,其病理状况包括微血管损伤、炎症和免疫异常。不同类型的 T 细胞可能通过细胞表面分子的上调和下调、异常释放促纤维化或促炎细胞因子以及与成纤维细胞的直接接触,导致 SSc 的血管炎和纤维化。这些 T 细胞主要是 CD4+T 细胞,包括 T 滤泡辅助(Tfh)细胞、调节性 T 细胞(Treg)、白细胞介素-17(IL-17)产生的 Th17 细胞、CD4 细胞毒性 T 淋巴细胞(CTL)和血管生成 T(Tang)细胞。除了早已确立的 Th1/Th2 失衡外,SSc 中还存在 Th17/Treg 失衡。这种失衡可能与 SSc 的异常免疫状态密切相关。越来越多的证据表明,T 细胞异常可能是 SSc 发病机制的关键。在治疗方面,针对 T 细胞的现有治疗方法,如免疫抑制治疗(他克莫司)、Janus 激酶(JAK)抑制剂和生物制剂(阿巴西普),已经取得了一些成功。其他非药物治疗方法,包括间充质干细胞(MSCs),具有广泛而复杂的作用机制,实际上包括 T 细胞调节。基于目前的证据,我们相信 T 细胞的研究将进一步加深我们对 SSc 发病机制的理解,并可能为 SSc 患者提供更有针对性的治疗选择。

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