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

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 forkh...

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Autores principales: Ren, Jiazi, Han, Lei, Tang, Jinyi, Liu, Yuanhua, Deng, Xiaoxue, Liu, Qiuyue, Hao, Pei, Feng, Xiaoming, Li, Bin, Hu, Hui, Wang, Haikun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534289/
https://www.ncbi.nlm.nih.gov/pubmed/31125332
http://dx.doi.org/10.1371/journal.pbio.3000270
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author Ren, Jiazi
Han, Lei
Tang, Jinyi
Liu, Yuanhua
Deng, Xiaoxue
Liu, Qiuyue
Hao, Pei
Feng, Xiaoming
Li, Bin
Hu, Hui
Wang, Haikun
author_facet Ren, Jiazi
Han, Lei
Tang, Jinyi
Liu, Yuanhua
Deng, Xiaoxue
Liu, Qiuyue
Hao, Pei
Feng, Xiaoming
Li, Bin
Hu, Hui
Wang, Haikun
author_sort Ren, Jiazi
collection PubMed
description 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.
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spelling pubmed-65342892019-06-05 Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function Ren, Jiazi Han, Lei Tang, Jinyi Liu, Yuanhua Deng, Xiaoxue Liu, Qiuyue Hao, Pei Feng, Xiaoming Li, Bin Hu, Hui Wang, Haikun PLoS Biol Research Article 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. Public Library of Science 2019-05-24 /pmc/articles/PMC6534289/ /pubmed/31125332 http://dx.doi.org/10.1371/journal.pbio.3000270 Text en © 2019 Ren et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ren, Jiazi
Han, Lei
Tang, Jinyi
Liu, Yuanhua
Deng, Xiaoxue
Liu, Qiuyue
Hao, Pei
Feng, Xiaoming
Li, Bin
Hu, Hui
Wang, Haikun
Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function
title Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function
title_full Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function
title_fullStr Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function
title_full_unstemmed Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function
title_short Foxp1 is critical for the maintenance of regulatory T-cell homeostasis and suppressive function
title_sort foxp1 is critical for the maintenance of regulatory t-cell homeostasis and suppressive function
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534289/
https://www.ncbi.nlm.nih.gov/pubmed/31125332
http://dx.doi.org/10.1371/journal.pbio.3000270
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