Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis

Takashi Sekiya, Ikkou Kashiwagi, Rei Yoshida, Tomohiro Fukaya, Rimpei Morita, Akihiro Kimura, Hiroshi Ichinose, Daniel Metzger, Pierre Chambon, Akihiko Yoshimura

Research output: Contribution to journalArticle

Abstract

Regulatory T cells (Treg cells) develop from progenitor thymocytes after the engagement of T cell antigen receptors (TCRs) with high-affinity ligands, but the underlying molecular mechanisms are still unclear. Here we show that the Nr4a nuclear receptors, which are encoded by immediate-early genes upregulated by TCR stimulation in thymocytes, have essential roles in Treg cell development. Mice that lacked all Nr4a factors could not produce Treg cells and died early owing to systemic autoimmunity. Nr4a receptors directly activated the promoter of the gene encoding the transcription factor Foxp3, and forced activation of Nr4a receptors bypassed low-strength TCR signaling to drive the Treg cell developmental program. Our results suggest that Nr4a receptors have key roles in determining CD4+ T cell fates in the thymus and thus contribute to immune homeostasis.

Original languageEnglish
JournalNature Immunology
DOIs
Publication statusAccepted/In press - 2013 Jan 20

ASJC Scopus subject areas

  • Immunology

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    Sekiya, T., Kashiwagi, I., Yoshida, R., Fukaya, T., Morita, R., Kimura, A., Ichinose, H., Metzger, D., Chambon, P., & Yoshimura, A. (Accepted/In press). Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis. Nature Immunology. https://doi.org/10.1038/ni.2520