GSE157693
Foxp3-specific deletion of CREB generates Th2 biased ST-2 positive regulatory T-cells with enhanced IL-10 production and suppressive capacity
Regulatory T cells (Tregs) are gatekeepers of immune homeostasis and characterized by expression of Foxp3, which maintains Treg identity. The transcriptional activator CREB critically stabilizes Foxp3 expression in vitro. Here we demonstrate that in mice with a Foxp3-specific knockout of CREB, Tregs show a reduced Foxp3 expression in vivo, but surprisingly enhanced expression of IL-13, IL-10, ST-2 and CREM. This rendered such Tregs highly suppressive in vitro and prevents disease activity in Th1 models like T cell mediated transfer colitis in an IL-10 dependent way. On the other hand, type 2 B cell responses were enhanced resulting in high IgE levels and susceptibility towards experimental asthma. Our data suggest that CREB expression in Tregs is important for the balance between Th1 and Th2 responses by regulating ST-2 and IL-10. Overall design: ATAC-seq profiles of  6-12 weeks old wild type (WT) and (Foxp3cre x CREB- flox) KO mice