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

Peter C. Cook, Heather Owen, Aimée M. Deaton, Jessica G. Borger, Sheila L. Brown, Thomas Clouaire, Gareth Rhys Jones, Lucy H. Jones, Rachel J. Lundie, Angela K. Marley, Vicky L. Morrison, Alexander T. Phythian-Adams, Elisabeth Wachter, Lauren M. Webb, Tara E. Sutherland, Graham D. Thomas, John R. Grainger, Jim Selfridge, Andrew N J McKenzie, Judith E. AllenSusanna C. Fagerholm, Rick M. Maizels, Alasdair C. Ivens, Adrian Bird, Andrew S. Macdonald

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    36 Citations (Scopus)

    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.

    Original languageEnglish
    Article number6920
    JournalNature Communications
    Volume6
    DOIs
    Publication statusPublished - 24 Apr 2015

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  • Cite this

    Cook, P. C., Owen, H., Deaton, A. M., Borger, J. G., Brown, S. L., Clouaire, T., Jones, G. R., Jones, L. H., Lundie, R. J., Marley, A. K., Morrison, V. L., Phythian-Adams, A. T., Wachter, E., Webb, L. M., Sutherland, T. E., Thomas, G. D., Grainger, J. R., Selfridge, J., McKenzie, A. N. J., ... Macdonald, A. S. (2015). A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells. Nature Communications, 6, [6920]. https://doi.org/10.1038/ncomms7920