The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells.
Bottom Line: Regulatory T cells (Tregs) have a central role in maintaining immune homoeostasis through various mechanisms.Nr4a2 binds to regulatory regions of Foxp3, where it mediates permissive histone modifications.Nr4a2-deficeint Tregs are prone to lose Foxp3 expression and have attenuated suppressive ability both in vitro and in vivo.
Affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.Show MeSH
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Mentions: We investigated the effect of Nr4a2 on the epigenetic status of the foxp3 promoter/enhancer. First, we isolated the total green fluorescence protein (GFP)-positive fractions from Nr4a2-virus- or control-virus-transduced CD4-SP cells, and performed native ChIP to compare their histone modification status with those of Tregs and naïve CD4+ T cells. As depicted in Figure 2a–c, Nr4a2 induced active histone modifications, histone H4-acetylation and histone H3K4-trimethylation, similar to the patterns in Tregs. H3K27-trimethylation, a repressive histone modification was not detected in both Tregs and Nr4a2-transduced T cells.
Affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.