Immunity
Volume 31, Issue 6, 18 December 2009, Pages 932-940
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Article
Development of Foxp3+ Regulatory T Cells Is Driven by the c-Rel Enhanceosome

https://doi.org/10.1016/j.immuni.2009.10.006Get rights and content
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Summary

Regulatory T (Treg) cells are essential for maintaining immune homeostasis. Although Foxp3 expression marks the commitment of progenitors to Treg cell lineage, how Treg cells are generated during lymphocyte development remains enigmatic. We report here that the c-Rel transcription factor controlled development of Treg cells by promoting the formation of a Foxp3-specific enhanceosome. This enhanceosome contained c-Rel, p65, NFAT, Smad, and CREB. Although Smad and CREB first bound to Foxp3 enhancers, they later moved to the promoter to form the c-Rel enhanceosome. c-Rel-deficient mice had up to 90% reductions of Treg cells compared to wild-type mice, and c-Rel-deficient T cells were compromised in Treg cell differentiation. Thus, Treg cell development is controlled by a c-Rel enhanceosome, and strategies targeting Rel-NF-κB can be effective for manipulating Treg cell function.

MOLIMMUNO
CELLIMMUNO

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