c-Rel is required for the development of thymic Foxp3(+) CD4 regulatory T cells
Details
Publication Year 2009-12-21,Volume 206,Issue #13,Page 3001-3014
Journal Title
JOURNAL OF EXPERIMENTAL MEDICINE
Publication Type
Journal Article
Abstract
During thymopoiesis, a unique program of gene expression promotes the development of CD4 regulatory T (T reg) cells. Although Foxp3 maintains a pattern of gene expression necessary for T reg cell function, other transcription factors are emerging as important determinants of T reg cell development. We show that the NF-kappa B transcription factor c-Rel is highly expressed in thymic T reg cells and that in c-rel(-/-) mice, thymic T reg cell numbers are markedly reduced as a result of a T cell-intrinsic defect that is manifest during thymocyte development. Although c-Rel is not essential for TGF-beta conversion of peripheral CD4(+)CD25(-) T cells into CD4(+)Foxp3(+) cells, it is required for optimal homeostatic expansion of peripheral T reg cells. Despite a lower number of peripheral T reg cells in c-rel(-/-) mice, the residual peripheral c-rel(-/-) T reg cells express normal levels of Foxp3, display a pattern of cell surface markers and gene expression similar to those of wild-type T reg cells, and effectively suppress effector T cell function in culture and in vivo. Collectively, our results indicate that c-Rel is important for both the thymic development and peripheral homeostatic proliferation of T reg cells.
Publisher
ROCKEFELLER UNIV PRESS
Keywords
NF-KAPPA-B; TRANSCRIPTION FACTOR FOXP3; GENOME-WIDE ANALYSIS; MICE LACKING; PERIPHERAL HOMEOSTASIS; CD28 COSTIMULATION; IMMUNE-RESPONSES; BCL-2 EXPRESSION; COMBINED ABSENCE; DENDRITIC CELLS
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Creation Date: 2009-12-21 12:00:00
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