Nature communications · 2015
A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Cook Peter C, Owen Heather, Deaton Aimée M, Borger Jessica G, Brown Sheila L, Clouaire Thomas, Jones Gareth-Rhys, Jones Lucy H, Lundie Rachel J, Marley Angela K, Morrison Vicky L, Phythian-Adams Alexander T, Wachter Elisabeth, Webb Lauren M, Sutherland Tara E, Thomas Graham D, Grainger John R, Selfridge Jim, McKenzie Andrew N J, Allen Judith E, Fagerholm Susanna C, Maizels Rick M, Ivens Alasdair C, Bird Adrian, MacDonald Andrew S
Аннотация
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.
Предметные рубрики MeSH
AllergensAnimalsCD4-Positive T-LymphocytesCell PolarityChromatin ImmunoprecipitationDNA MethylationDNA-Binding ProteinsDendritic CellsEnzyme-Linked Immunosorbent AssayEpigenesis, GeneticFlow CytometryGene Expression RegulationHypersensitivityLymphocyte ActivationMiceMice, KnockoutPyroglyphidaeRNA, MessengerReverse Transcriptase Polymerase Chain ReactionSchistosoma mansoniSchistosomiasis mansoniTh2 Cells