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

The NF‐κB/Rel family member c‐Rel was described to be required for the development of T_H1 responses. However, the role of c‐Rel in the differentiation of T_H17 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 T_H17 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 CD4⁺ 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.