Isomura, I., Palmer, S., Grumont, R. J., Bunting, K., Hoyne, G. F., Wilkinson, N., Banerjee, A., Proietto, A., Gugasyan, R., Wu, L., McNally, A., Steptoe, R. J., Thomas, R., Shannon, M. F., & Gerondakis, S. (2009). c-Rel is required for the development of thymic Foxp3 CD4 regulatory T cells. Journal of Experimental Medicine, 206 (13), 3001-3014.
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-κB 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-β 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.
Peer-reviewed, T cells, CD4, regulatory T cells, Foxp3, c-Rel