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

被引:64
作者
Cook, Peter C. [1 ]
Owen, Heather [3 ]
Deaton, Aimee M. [2 ]
Borger, Jessica G. [3 ]
Brown, Sheila L. [1 ]
Clouaire, Thomas [2 ]
Jones, Gareth-Rhys [1 ]
Jones, Lucy H. [3 ]
Lundie, Rachel J. [3 ]
Marley, Angela K. [3 ]
Morrison, Vicky L. [4 ]
Phythian-Adams, Alexander T. [1 ]
Wachter, Elisabeth [2 ]
Webb, Lauren M. [1 ]
Sutherland, Tara E. [3 ]
Thomas, Graham D. [3 ]
Grainger, John R. [1 ]
Selfridge, Jim [2 ]
McKenzie, Andrew N. J. [5 ]
Allen, Judith E. [3 ]
Fagerholm, Susanna C. [4 ]
Maizels, Rick M. [3 ]
Ivens, Alasdair C. [3 ]
Bird, Adrian [2 ]
MacDonald, Andrew S. [1 ]
机构
[1] Univ Manchester, Manchester Collaborat Ctr Inflammat Res, Manchester M3 9NT, Lancs, England
[2] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3BF, Midlothian, Scotland
[3] Univ Edinburgh, Inst Immunol & Infect Res, Sch Biol Sci, Ctr Immun Infect & Evolut, Edinburgh EH9 3FL, Midlothian, Scotland
[4] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland
[5] MRC, Mol Biol Lab, Cambridge CB2 0QH, England
基金
英国惠康基金;
关键词
IN-VIVO; EPIGENETIC CONTROL; TYPE-2; IMMUNITY; CUTTING EDGE; ALLERGIC INFLAMMATION; IL-17; INDUCTION; DNA METHYLATION; T-CELLS; RESPONSES; DIFFERENTIATION;
D O I
10.1038/ncomms7920
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:11
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