c-Rel is crucial for the induction of Foxp3+ regulatory CD4 + T cells but not TH17 cells

Abstract

The NF-κB/Rel family member c-Rel was described to be required for the development of TH1 responses. However, the role of c-Rel in the differentiation of TH17 and regulatory CD4+Foxp3 + T cells (Treg) remains obscure. Here, we show that in the absence of c-Rel, in vitro differentiation of pro-inflammatory TH17 cells is normal. In contrast, generation of inducible Treg (iTreg) within c-Rel-deficient CD4+ T cells was severely hampered and correlated to reduced numbers of Foxp3+ T cells in vivo. Mechanistically, in vitro conversion of naive CD41 T cells into iTreg was crucially dependent on c-Rel-mediated synthesis of endogenous IL-2. The addition of exogenous IL-2 was sufficient to rescue the development of c-Rel-deficient iTreg. Thus, c-Rel is essential for the development of Foxp3+ Treg but not for T H17 cells via regulating the production of IL-2. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.