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

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

Author information

1
Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M3 9NT, UK.
2
Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
3
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, UK.
4
Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY UK.
5
Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 0QH UK.

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.

PMID:
25908537
PMCID:
PMC4413429
DOI:
10.1038/ncomms7920
[Indexed for MEDLINE]
Free PMC Article

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