Jan 22, 2013

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

Nature Immunology
Takashi SekiyaAkihiko Yoshimura

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.

  • References48
  • Citations95

References

  • References48
  • Citations95

Citations

Mentioned in this Paper

T-Lymphocyte
Immune System Diseases
Cosuppression
Receptors, Antigen
Neoplasm of Uncertain or Unknown Behavior of Thymus
Thymocyte
Thyroid Hormone Receptor
Disease of Thymus Gland
Promoter
Foxp3 protein, mouse

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