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: Because Nr4a mediates various physiological events, some in a redundant manner and others in a non-redundant manner, we compared the ability of the three family members to induce Foxp3. Importantly, both Nr4a1 and Nr4a3 have also been reported to be abundant in Tregs31 and inducible by TCR stimulation32. We found that Nr4a1 rarely induced Foxp3, whereas Nr4a3 did so to an intermediate degree (Fig. 3a,b), despite the expression levels of these proteins were similar (Supplementary Fig. S3a).
Affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.