GSE66198
A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells [ChIP-Seq]
Dendritic cells (DCs) direct CD4+ T cell differentiation into distinct T helper (Th) subsets that are vital for protection against diverse types of infection.  However, the mechanisms employed by DCs to initiate Th2 responses, which are important for immunity to helminth infection as well as being a major contributor to allergic disease, remain poorly understood.  We demonstrate a key role for methyl-CpG-binding domain-2 (Mbd2), a protein that links DNA methylation to repressive chromatin structure, in regulating expression of a range of genes that are associated with optimal DC activation and function. In the absence of Mbd2, DCs displayed reduced phenotypic activation and a dramatically impaired ability to promote Th2 immunity against either helminths or allergens, while their induction of Th1/17 responses remained intact. These data reveal a novel epigenetic mechanism that is integral to DC promotion of CD4+ T cell responses, particularly in Th2 settings, and identify methyl-CpG-binding proteins and the genes that they control as potential therapeutic targets for type-2 inflammation. Overall design: H3K9,K14ac (H3ac) occupancy was analysed by ChIP-Seq for control (wt) or Mbd2 -/- (DEL) dendritic cells (DC). Input DNA for each cell line was also sequenced alongside.