A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells

Nat Commun. 2015 Apr 24;6:6920. doi: 10.1038/ncomms7920.

Abstract

Dendritic cells (DCs) direct CD4(+) T-cell differentiation into diverse helper (Th) subsets that are required for protection against varied infections. However, the mechanisms used by DCs to promote Th2 responses, which are important both for immunity to helminth infection and in allergic disease, are currently poorly understood. We demonstrate a key role for the protein methyl-CpG-binding domain-2 (Mbd2), which 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 display reduced phenotypic activation and a markedly impaired capacity to initiate Th2 immunity against helminths or allergens. These data identify an epigenetic mechanism that is central to the activation of CD4(+) T-cell responses by DCs, particularly in Th2 settings, and reveal methyl-CpG-binding proteins and the genes under their control as possible therapeutic targets for type-2 inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Polarity
  • Chromatin Immunoprecipitation
  • DNA Methylation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Dendritic Cells / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Epigenesis, Genetic
  • Flow Cytometry
  • Gene Expression Regulation / genetics*
  • Hypersensitivity / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • Pyroglyphidae / immunology
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Schistosoma mansoni / immunology
  • Schistosomiasis mansoni / immunology
  • Th2 Cells / immunology*

Substances

  • Allergens
  • DNA-Binding Proteins
  • Mbd2 protein, mouse
  • RNA, Messenger