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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Yang BH,Wang K,Wan S,Liang Y,Yuan X,Dong Y,Cho S,Xu W,Jepsen K,Feng GS,Lu LF,Xue HH,Fu Wdoi
10.1016/j.celrep.2019.05.061subject
Has Abstractpub_date
2019-06-18 00:00:00pages
3629-3645.e6issue
12issn
2211-1247pii
S2211-1247(19)30690-4journal_volume
27pub_type
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