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. Allen; Susanna C. Fagerholm; Rick M. Maizels; Alasdair C. Ivens; Adrian Bird; Andrew S. Macdonald

doi:10.1038/ncomms7920

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 (Lead / Corresponding author)

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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.

Original language	English
Article number	6920
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7920
Publication status	Published - 24 Apr 2015

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology
General Chemistry
General Physics and Astronomy

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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, Article 6920. https://doi.org/10.1038/ncomms7920

@article{1833604ec15949cdafaecb4e6f184b61,

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

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.",

author = "Cook, {Peter C.} and Heather Owen and Deaton, {Aim{\'e}e M.} and Borger, {Jessica G.} and Brown, {Sheila L.} and Thomas Clouaire 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 Elisabeth Wachter and Webb, {Lauren M.} and Sutherland, {Tara E.} and Thomas, {Graham D.} and Grainger, {John R.} and Jim Selfridge and McKenzie, {Andrew N J} and Allen, {Judith E.} and Fagerholm, {Susanna C.} and Maizels, {Rick M.} and Ivens, {Alasdair C.} and Adrian Bird and Macdonald, {Andrew S.}",

year = "2015",

month = apr,

day = "24",

doi = "10.1038/ncomms7920",

language = "English",

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Cook, PC, Owen, H, Deaton, AM, Borger, JG, Brown, SL, Clouaire, T, Jones, GR, Jones, LH, Lundie, RJ, Marley, AK, Morrison, VL, Phythian-Adams, AT, Wachter, E, Webb, LM, Sutherland, TE, Thomas, GD, Grainger, JR, Selfridge, J, McKenzie, ANJ, Allen, JE, Fagerholm, SC, Maizels, RM, Ivens, AC, Bird, A & Macdonald, AS 2015, 'A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells', Nature Communications, vol. 6, 6920. https://doi.org/10.1038/ncomms7920

TY - JOUR

T1 - A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells

AU - Cook, Peter C.

AU - Owen, Heather

AU - Deaton, Aimée M.

AU - Borger, Jessica G.

AU - Brown, Sheila L.

AU - Clouaire, Thomas

AU - Jones, Gareth Rhys

AU - Jones, Lucy H.

AU - Lundie, Rachel J.

AU - Marley, Angela K.

AU - Morrison, Vicky L.

AU - Phythian-Adams, Alexander T.

AU - Wachter, Elisabeth

AU - Webb, Lauren M.

AU - Sutherland, Tara E.

AU - Thomas, Graham D.

AU - Grainger, John R.

AU - Selfridge, Jim

AU - McKenzie, Andrew N J

AU - Allen, Judith E.

AU - Fagerholm, Susanna C.

AU - Maizels, Rick M.

AU - Ivens, Alasdair C.

AU - Bird, Adrian

AU - Macdonald, Andrew S.

PY - 2015/4/24

Y1 - 2015/4/24

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms7920

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C2 - 25908537

AN - SCOPUS:84928805959

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 6920

ER -

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

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ASJC Scopus subject areas

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