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

Cook, P. C. et al. (2015) A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells. Nature Communications, 6, 6920. (doi: 10.1038/ncomms7920) (PMID:25908537) (PMCID:PMC4413429)

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: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Morrison, Dr Vicky and Maizels, Professor Rick
• Authors: 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., Allen, J. E., Fagerholm, S. C., Maizels, R. M., Ivens, A. C., Bird, A., and MacDonald, A. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Publishing Group
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in Nature Communications 6:6920
• Publisher Policy: Reproduced under a Creative Commons License