1. TCF1 and LEF1 Control Treg Competitive Survival and Tfr Development to Prevent Autoimmune Diseases.
- Author
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Yang BH, Wang K, Wan S, Liang Y, Yuan X, Dong Y, Cho S, Xu W, Jepsen K, Feng GS, Lu LF, Xue HH, and Fu W
- Subjects
- Animals, Autoimmune Diseases immunology, Autoimmune Diseases pathology, Cell Differentiation, Female, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Autoimmune Diseases prevention & control, Autoimmunity immunology, Germinal Center immunology, Hepatocyte Nuclear Factor 1-alpha physiology, Lymphoid Enhancer-Binding Factor 1 physiology, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Regulatory immunology
- Abstract
CD4
+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg's differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient expression of TCF1 and LEF1 distinguishes Tregs into three distinct subpopulations, particularly highlighting a subset of activated Treg (aTreg) cells. Treg-specific ablation of TCF1 and LEF1 renders the mice susceptible to systemic autoimmunity. TCF1 and LEF1 are dispensable for Treg's suppressive capacity but essential for maintaining a normal aTreg pool and promoting Treg's competitive survival. As a consequence, the development of T follicular regulatory (Tfr) cells, which are a subset of aTreg, is abolished in TCF1/LEF1-conditional knockout mice, leading to unrestrained T follicular helper (Tfh) and germinal center B cell responses. Thus, TCF1 and LEF1 act redundantly to control the maintenance and functional specification of Treg subsets to prevent autoimmunity., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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