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. Jackson-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

Research output: Contribution to journalArticleResearchpeer-review

30 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
Number of pages11
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 24 Apr 2015
Externally publishedYes

Cite this

Cook, Peter C. ; Owen, Heather ; Deaton, Aimée M. ; Borger, Jessica G. ; Brown, Sheila L. ; Clouaire, Thomas ; Jones, Gareth Rhys ; Jackson-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. / A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells. In: Nature Communications. 2015 ; Vol. 6.
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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 Jackson-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 = "4",
day = "24",
doi = "10.1038/ncomms7920",
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journal = "Nature Communications",
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Cook, PC, Owen, H, Deaton, AM, Borger, JG, Brown, SL, Clouaire, T, Jones, GR, Jackson-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

A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells. / Cook, Peter C.; Owen, Heather; Deaton, Aimée M.; Borger, Jessica G.; Brown, Sheila L.; Clouaire, Thomas; Jones, Gareth Rhys; Jackson-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.

In: Nature Communications, Vol. 6, 6920, 24.04.2015.

Research output: Contribution to journalArticleResearchpeer-review

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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 - Jackson-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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