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

Abstract:

:Regulatory T cells (T(reg) 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 T(reg) cell development. Mice that lacked all Nr4a factors could not produce T(reg) 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 T(reg) 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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Sekiya T,Kashiwagi I,Yoshida R,Fukaya T,Morita R,Kimura A,Ichinose H,Metzger D,Chambon P,Yoshimura A

doi

10.1038/ni.2520

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

230-7

issue

3

eissn

1529-2908

issn

1529-2916

pii

ni.2520

journal_volume

14

pub_type

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