Transcription factor IRF8 controls Thl-like regulatory T-cell function

Recent studies have suggested that regulatory T （Treg） cells comprise a heterogeneous population that regulates various aspects of the immune response, and that Treg cells use the factors that are expressed in their target cells to regulate them. We searched for factors that regulate Thl response in Treg cells using a meta-analysis. In the process, we discovered that transcription factor interferon regulatory factor 8 （I RF8） was selectively expressed in Treg and Th I cells. IRF8-deficient Treg cells showed defective expression of CXCR3 and aberrant expression of the 114 and 1117genes. Upon treatment with alpha galactosyI-C18-ceramide （aGaI-C18-Cer）, IRF8-deficient mice showed defective Treg cell recruitment in the liver. Eliciting Thl immune response by anti-CD40 antibody injection in mice induced IRF8 expression in Treg cells. The expression of IRF8 was induced by Foxp3 in Treg cells, IRF8 had no effect on T-bet expression in Treg and vice versa. Thus, our results strongly suggest that IRF8 controls Thl immune response in Treg cells independent of T-bet.