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