INSERM UMRs 938, Centre de Recherche Saint-Antoine, AP-HP, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Université, 75012, Paris, France.
Sorbonne Université, Paris, France.
J Transl Med. 2021 Aug 30;19(1):375. doi: 10.1186/s12967-021-03049-0.
Systemic sclerosis is an autoimmune disease characterized by excessive dermal fibrosis with progression to internal organs, vascular impairment and immune dysregulation evidenced by the infiltration of inflammatory cells in affected tissues and the production of auto antibodies. While the pathogenesis remains unclear, several data highlight that T and B cells deregulation is implicated in the disease pathogenesis. Over the last decade, aberrant responses of circulating T follicular helper cells, a subset of CD4 T cells which are able to localise predominantly in the B cell follicles through a high level of chemokine receptor CXCR5 expression are described in pathogenesis of several autoimmune diseases and chronic graft-versus-host-disease. In the present review, we summarized the observed alteration of number and frequency of circulating T follicular helper cells in systemic sclerosis. We described their role in aberrant B cell activation and differentiation though interleukine-21 secretion. We also clarified T follicular helper-like cells involvement in fibrogenesis in both human and mouse model. Finally, because T follicular helper cells are involved in both fibrosis and autoimmune abnormalities in systemic sclerosis patients, we presented the different strategies could be used to target T follicular helper cells in systemic sclerosis, the therapeutic trials currently being carried out and the future perspectives from other auto-immune diseases and graft-versus-host-disease models.
系统性硬化症是一种自身免疫性疾病，其特征是皮肤过度纤维化，进而发展为内部器官、血管损伤和免疫失调，表现为受影响组织中炎症细胞的浸润和自身抗体的产生。虽然发病机制尚不清楚，但有几项数据表明 T 细胞和 B 细胞的失调与疾病的发病机制有关。在过去的十年中，人们描述了循环滤泡辅助性 T 细胞（一种能够通过高水平表达趋化因子受体 CXCR5 主要定位于 B 细胞滤泡的 CD4 T 细胞亚群）的异常反应在几种自身免疫性疾病和慢性移植物抗宿主病的发病机制中的作用。在本综述中，我们总结了系统性硬化症中循环滤泡辅助性 T 细胞数量和频率的变化。我们描述了它们通过分泌白细胞介素-21 在异常 B 细胞激活和分化中的作用。我们还阐明了滤泡辅助样细胞在人类和小鼠模型中的纤维化中的作用。最后，由于滤泡辅助性 T 细胞参与系统性硬化症患者的纤维化和自身免疫异常，我们提出了可以用来靶向系统性硬化症中滤泡辅助性 T 细胞的不同策略，目前正在进行的治疗试验以及其他自身免疫性疾病和移植物抗宿主病模型的未来前景。
