University of Tsukuba, Tsukuba, Japan.
Arthritis Rheumatol. 2018 May;70(5):653-661. doi: 10.1002/art.40398. Epub 2018 Mar 13.
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the joint synovium and infiltration by activated inflammatory cells. CD4+ T cells form a large proportion of the inflammatory cells invading the synovial tissue, and are involved in the RA pathologic process. In general, CD4+ T cells differentiate into various T helper cell subsets and acquire the functional properties to respond to specific pathogens, and also mediate some autoimmune disorders such as RA. Because the differentiation of T helper cell subsets is determined by the expression of specific transcription factors in response to the cytokine environment, these transcription factors are considered to have a role in the pathology of RA. Treg cells control an excess of T cell-mediated immune response, and the transcription factor FoxP3 is critical for the differentiation and function of Treg cells. Treg cell dysfunction can result in the development of systemic autoimmunity. In this review, we summarize how the expression of transcription factors modulates T helper cell immune responses and the development of autoimmune diseases, especially in RA. Understanding the role of transcription factors in the pathogenesis of autoimmunity may lead to novel therapeutic strategies to control the differentiation and function of both T helper cells and Treg cells.
类风湿关节炎(RA)是一种自身免疫性疾病,其特征为关节滑膜的慢性炎症和活化炎症细胞的浸润。CD4+T 细胞构成浸润滑膜组织的炎症细胞的很大一部分,并且参与 RA 的病理过程。一般来说,CD4+T 细胞分化为各种辅助性 T 细胞亚群,并获得响应特定病原体的功能特性,也介导一些自身免疫性疾病,如 RA。由于辅助性 T 细胞亚群的分化是由细胞因子环境中特定转录因子的表达决定的,因此这些转录因子被认为在 RA 的病理学中具有作用。调节性 T 细胞(Treg 细胞)控制 T 细胞介导的免疫反应的过度,转录因子 FoxP3 对 Treg 细胞的分化和功能至关重要。Treg 细胞功能障碍可导致全身性自身免疫的发展。在这篇综述中,我们总结了转录因子的表达如何调节辅助性 T 细胞免疫反应和自身免疫性疾病的发展,尤其是在 RA 中。了解转录因子在自身免疫发病机制中的作用可能会导致控制辅助性 T 细胞和 Treg 细胞分化和功能的新的治疗策略。