Regulatory T cells in multiple sclerosis and myasthenia gravis.
Regulatory T cells in multiple sclerosis and myasthenia gravis.
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多发性硬化症和重症肌无力的调节性T细胞。
DOI：
10.1186/s12974-017-0892-8
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发表时间：
2017-06-09
影响因子：
9.3
通讯作者：
Prabhakar BS
中科院分区：
文献类型：
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作者：
Danikowski KM;Jayaraman S;Prabhakar BS
多发性硬化症（MS）是一种中枢神经系统的慢性衰弱性疾病，主要由遗传易感个体中对神经元抗原具有特异性的T淋巴细胞介导。另一方面，重症肌无力（MG）主要涉及乙酰胆碱受体特异性抗体对神经肌肉接头的破坏。这两种自身免疫性疾病被认为是由于自身耐受性的丧失，这使得自身反应性淋巴细胞的发展和功能。虽然在这些和其他自身免疫性疾病中受损的自身耐受性的机制尚未完全阐明，但一种可能性是T调节细胞（T细胞）的数量、功能和/或迁移缺陷。认为T细胞在维持外周免疫耐受中起关键作用。据信，T细胞通过抑制介导自身免疫应答的效应CD 4 + T细胞亚群来发挥功能。TGFs上抑制性和迁移性标志物的失调与MS和MG的发病机制有关。例如，在Treg抑制性标志物CTLA-4和CD 25中发现了遗传异常，而其他人则显示FoxP 3和IL-10的表达降低。此外，在MS和MG患者中已经注意到由T效应物分泌的促炎细胞因子如IL-6、IL-17和IFN-γ水平升高。这篇综述提供了几种治疗策略，这些策略已被证明是有效的，或被提议作为潜在的治疗方法来恢复各种Treg亚群的功能，包括Tr 1，iTr 35，nT细胞和iT细胞。聚焦于增强Treg功能的策略在细胞因子TGF-β、IDO、白细胞介素10、27和35以及配体Jagged-1和OX 40 L中发现重要性。同样，影响Treg迁移的策略涉及趋化因子CCL 17和CXCL 11。在实验性自身免疫性脑脊髓炎（EAE）和实验性自身免疫性重症肌无力（EAMG）的临床前动物模型中，已经显示了几种策略来改善疾病，因此对于治疗MS或MG患者似乎是有希望的。
Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs). Tregs are thought to play a critical role in the maintenance of peripheral immune tolerance. It is believed that Tregs function by suppressing the effector CD4+ T cell subsets that mediate autoimmune responses. Dysregulation of suppressive and migratory markers on Tregs have been linked to the pathogenesis of both MS and MG. For example, genetic abnormalities have been found in Treg suppressive markers CTLA-4 and CD25, while others have shown a decreased expression of FoxP3 and IL-10. Furthermore, elevated levels of pro-inflammatory cytokines such as IL-6, IL-17, and IFN-γ secreted by T effectors have been noted in MS and MG patients. This review provides several strategies of treatment which have been shown to be effective or are proposed as potential therapies to restore the function of various Treg subsets including Tr1, iTr35, nTregs, and iTregs. Strategies focusing on enhancing the Treg function find importance in cytokines TGF-β, IDO, interleukins 10, 27, and 35, and ligands Jagged-1 and OX40L. Likewise, strategies which affect Treg migration involve chemokines CCL17 and CXCL11. In pre-clinical animal models of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune myasthenia gravis (EAMG), several strategies have been shown to ameliorate the disease and thus appear promising for treating patients with MS or MG.