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健康与自身免疫性疾病中辅助性 T 细胞 17 分化的转录调控因子。

Transcriptional Regulators of T Helper 17 Cell Differentiation in Health and Autoimmune Diseases.

机构信息

Neuroimmunology Unit, IRCSS Fondazione Santa Lucia, Rome, Italy.

Department of Biology and Biotechnology Charles Darwin, Sapienza University, Rome, Italy.

出版信息

Front Immunol. 2020 Mar 12;11:348. doi: 10.3389/fimmu.2020.00348. eCollection 2020.

Abstract

T helper (Th) 17 cells are a subtype of CD4 T lymphocytes characterized by the expression of retinoic acid-receptor (RAR)-related orphan receptor (ROR)γt transcription factor, encoded by gene . These cells are implicated in the pathology of autoimmune inflammatory disorders as well as in the clearance of extracellular infections. The main function of Th17 cells is the production of cytokine called interleukin (IL)-17A. This review highlights recent advances in mechanisms regulating transcription of IL-17A. In particular, we described the lineage defining transcription factor RORγt and other factors that regulate transcription of or by interacting with RORγt or by binding their specific DNA regions, which may positively or negatively influence their expression. Moreover, we reported the eventual involvement of those factors in Th17-related diseases, such as multiple sclerosis, rheumatoid arthritis, psoriasis, and Crohn's disease, characterized by an exaggerated Th17 response. Finally, we discussed the potential new therapeutic approaches for Th17-related diseases targeting these transcription factors. The wide knowledge of transcriptional regulators of Th17 cells is crucial for the better understanding of the pathogenic role of these cells and for development of therapeutic strategies aimed at fighting Th17-related diseases.

摘要

辅助性 T 细胞 17(Th17)细胞是一种 CD4 T 淋巴细胞亚群,其特征在于表达维甲酸受体(RAR)相关孤儿受体(ROR)γt 转录因子,由基因编码。这些细胞与自身免疫性炎症性疾病的发病机制以及细胞外感染的清除有关。Th17 细胞的主要功能是产生细胞因子白细胞介素(IL)-17A。本综述强调了调节 IL-17A 转录的机制的最新进展。特别是,我们描述了谱系定义转录因子 RORγt 以及其他通过与 RORγt 相互作用或结合其特定 DNA 区域来调节 或 转录的因子,这些因子可能正面或负面影响其表达。此外,我们报告了这些因子最终参与与 Th17 相关的疾病,如多发性硬化症、类风湿性关节炎、银屑病和克罗恩病,其特征是 Th17 反应过度。最后,我们讨论了针对这些转录因子的针对 Th17 相关疾病的潜在新的治疗方法。Th17 细胞的转录调节剂的广泛知识对于更好地理解这些细胞的致病作用以及开发旨在对抗 Th17 相关疾病的治疗策略至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7080699/8a9f982388fc/fimmu-11-00348-g0001.jpg

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