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Development of Foxp3(+) regulatory t cells is driven by the c-Rel enhanceosome.

ABSTRACT: 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-kappaB can be effective for manipulating Treg cell function.

SUBMITTER: Ruan Q

PROVIDER: S-EPMC2807990 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Development of Foxp3(+) regulatory t cells is driven by the c-Rel enhanceosome.

Ruan Qingguo Q Kameswaran Vasumathi V Tone Yukiko Y Li Li L Liou Hsiou-Chi HC Greene Mark I MI Tone Masahide M Chen Youhai H YH

Immunity 20091201 6

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 enhance ...[more]

PMID: 20064450

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