美国哈佛医学院Ana C. Anderson研究团队发现，转录因子TCF1与RORγt结合并协调一个调控网络来决定稳态Th17细胞的状态。相关论文于2024年10月23日在线发表在《免疫》杂志上。

研究人员发现促炎细胞因子白细胞介素（IL）-23能够降低转录因子T细胞因子1（TCF1）的表达。在成熟T细胞中条件性删除TCF1增强了T辅助细胞（Th）17细胞的促炎潜力，即使在缺乏IL-23受体信号的情况下，也赋予了稳态Th17细胞促炎潜力。

相反，持续表达TCF1降低了Th17细胞的促炎潜力。从机制上讲，TCF1与RORγt结合，从而干扰其促炎功能，并协调一个调控网络，决定了Th17细胞的状态。

这些发现确定了TCF1作为Th17细胞状态的主要决定因子，为开发针对Th17驱动的炎症疾病的治疗提供了重要的见解。

据了解，Th17细胞涵盖了一系列细胞状态，包括维持组织稳态功能的细胞和能够引发自身免疫组织损伤的促炎细胞。识别决定Th17细胞状态的调控因子可以找到控制组织炎症和恢复稳态的方法。

附：英文原文

Title: Transcription factor TCF1 binds to RORγt and orchestrates a regulatory network that determines homeostatic Th17 cell state

Author: Davide Mangani, Ayshwarya Subramanian, Linglin Huang, Hanning Cheng, S. Harsha Krovi, Yufan Wu, Dandan Yang, Thais G. Moreira, Giulia Escobar, Alexandra Schnell, Karen O. Dixon, Rajesh K. Krishnan, Vasundhara Singh, Raymond A. Sobel, Howard L. Weiner, Vijay K. Kuchroo, Ana C. Anderson

Issue&Volume: 2024-10-23

Abstract: T helper (Th) 17 cells encompass a spectrum of cell states, including cells that maintain homeostatic tissue functions and pro-inflammatory cells that can drive autoimmune tissue damage. Identifying regulators that determine Th17 cell states can identify ways to control tissue inflammation and restore homeostasis. Here, we found that interleukin (IL)-23, a cytokine critical for inducing pro-inflammatory Th17 cells, decreased transcription factor T cell factor 1 (TCF1) expression. Conditional deletion of TCF1 in mature T cells increased the pro-inflammatory potential of Th17 cells, even in the absence of IL-23 receptor signaling, and conferred pro-inflammatory potential to homeostatic Th17 cells. Conversely, sustained TCF1 expression decreased pro-inflammatory Th17 potential. Mechanistically, TCF1 bound to RORγt, thereby interfering with its pro-inflammatory functions, and orchestrated a regulatory network that determined Th17 cell state. Our findings identify TCF1 as a major determinant of Th17 cell state and provide important insight for the development of therapies for Th17-driven inflammatory diseases.

DOI: 10.1016/j.immuni.2024.09.017

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00480-1