The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells Journal Article
| Authors: | Sekiya, T.; Kashiwagi, I.; Inoue, N.; Morita, R.; Hori, S.; Waldmann, H.; Rudensky, A. Y.; Ichinose, H.; Metzger, D.; Chambon, P.; Yoshimura, A. |
| Article Title: | The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells |
| Abstract: | Regulatory T cells (Tregs) have a central role in maintaining immune homoeostasis through various mechanisms. Although the Forkhead transcription factor Foxp3 defines the Treg cell lineage and functions, the molecular mechanisms of Foxp3 induction and maintenance remain elusive. Here we show that Foxp3 is one of the direct targets of Nr4a2. Nr4a2 binds to regulatory regions of Foxp3, where it mediates permissive histone modifications. Ectopic expression of Nr4a2 imparts Treg-like suppressive activity to naïve CD4+ T cells by inducing Foxp3 and by repressing cytokine production, including interferon-γ and interleukin-2. Deletion of Nr4a2 in T cells attenuates induction of Tregs and causes aberrant induction of Th1, leading to the exacerbation of colitis. Nr4a2-deficeint Tregs are prone to lose Foxp3 expression and have attenuated suppressive ability both in vitro and in vivo. Thus, Nr4a2 has the ability to maintain T-cell homoeostasis by regulating induction, maintenance and suppressor functions of Tregs, and by repression of aberrant Th1 induction. © 2011 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | protein expression; polymerase chain reaction; transcription factor foxp3; protein analysis; interleukin 2; enzyme inhibition; protein targeting; protein binding; cell differentiation; in vitro study; regulatory t lymphocyte; gamma interferon; messenger rna; epigenetics; chromatin immunoprecipitation; quantitative analysis; cd4+ t lymphocyte; colitis; cytokine production; th1 cell; animal cell culture; disease exacerbation; leukocyte; histone modification; nuclear receptor related factor 1; homeostasis and regulation; lamina propria |
| Journal Title: | Nature Communications |
| Volume: | 2 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2011-01-01 |
| Start Page: | 269 |
| Language: | English |
| DOI: | 10.1038/ncomms1272 |
| PROVIDER: | scopus |
| PMCID: | PMC3104557 |
| PUBMED: | 21468021 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 23 June 2011" - "Art. No.: 269" - "Source: Scopus" |
