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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1783421381378048000 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6534289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT renjiazi foxp1iscriticalforthemaintenanceofregulatorytcellhomeostasisandsuppressivefunction AT hanlei foxp1iscriticalforthemaintenanceofregulatorytcellhomeostasisandsuppressivefunction AT tangjinyi foxp1iscriticalforthemaintenanceofregulatorytcellhomeostasisandsuppressivefunction AT liuyuanhua foxp1iscriticalforthemaintenanceofregulatorytcellhomeostasisandsuppressivefunction AT dengxiaoxue foxp1iscriticalforthemaintenanceofregulatorytcellhomeostasisandsuppressivefunction AT liuqiuyue foxp1iscriticalforthemaintenanceofregulatorytcellhomeostasisandsuppressivefunction AT haopei foxp1iscriticalforthemaintenanceofregulatorytcellhomeostasisandsuppressivefunction AT fengxiaoming foxp1iscriticalforthemaintenanceofregulatorytcellhomeostasisandsuppressivefunction AT libin foxp1iscriticalforthemaintenanceofregulatorytcellhomeostasisandsuppressivefunction AT huhui foxp1iscriticalforthemaintenanceofregulatorytcellhomeostasisandsuppressivefunction AT wanghaikun foxp1iscriticalforthemaintenanceofregulatorytcellhomeostasisandsuppressivefunction |