Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function

Ren, Jiazi and Han, Lei and Tang, Jinyi and Liu, Yuanhua and Deng, Xiaoxue and Liu, Qiuyue and Hao, Pei and Feng, Xiaoming and Li, Bin and Hu, Hui and Wang, Haikun and Oliver, Paula M. (2019) Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function. PLOS Biology, 17 (5). e3000270. ISSN 1545-7885

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Abstract

Regulatory T (Treg) cells play central roles in maintaining immune homeostasis and self-tolerance. However, the molecular mechanisms underlying Treg cell homeostasis and suppressive function are still not fully understood. Here, we report that the deletion of another P subfamily members of the forkhead box (Foxp) subfamily member Foxp1 in Treg cells led to increased numbers of activated Treg (aTreg) cells at the expense of quiescent Treg cells, and also resulted in impaired Treg suppressive function. Mice with Foxp1-deficient Treg cells developed spontaneous inflammatory disease with age; they also had more severe inflammatory disease in colitis and experimental autoimmune encephalomyelitis (EAE) models. Mechanistically, we found that Foxp1 bound to the conserved noncoding sequence 2 (CNS2) element of the Foxp3 locus and helped maintain Treg suppressive function by stabilizing the Foxp3 expression. Furthermore, we found that Foxp1 and Foxp3 coordinated the regulation of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression levels. Taken together, our study demonstrates that Foxp1 plays critical roles in both maintaining Treg cell quiescence during homeostasis and regulating Treg suppressive function.

Item Type: Article
Subjects: Bengali Archive > Biological Science
Depositing User: Unnamed user with email support@bengaliarchive.com
Date Deposited: 27 Jan 2023 07:52
Last Modified: 29 Apr 2024 07:52
URI: http://science.archiveopenbook.com/id/eprint/14

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