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

Cook, Peter C and Owen, Heather and Deaton, Aimée M and Borger, Jessica G and Brown, Sheila L and Clouaire, Thomas and Jones, Gareth-Rhys and Jones, Lucy H and Lundie, Rachel J and Marley, Angela K and Morrison, Vicky L and Phythian-Adams, Alexander T and Wachter, Elisabeth and Webb, Lauren M and Sutherland, Tara E and Thomas, Graham D and Grainger, John R and Selfridge, Jim and McKenzie, Andrew N J and Allen, Judith E and Fagerholm, Susanna C and Maizels, Rick M and Ivens, Alasdair C and Bird, Adrian and MacDonald, Andrew S (2015) A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells. Nature Communications, 6. ISSN 2041-1723

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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.

Item Type:
Journal Article
Journal or Publication Title:
Nature Communications
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/3100
Subjects:
ID Code:
125053
Deposited By:
Deposited On:
09 May 2018 14:06
Refereed?:
Yes
Published?:
Published
Last Modified:
26 May 2020 06:42