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

Peter Cook; Heather Owen; Aimée M Deaton; Jessica G Borger; Sheila Brown; Thomas Clouaire; Gareth-Rhys Jones; Lucy H Jones; Rachel J Lundie; Angela K Marley; Vicky L Morrison; Alexander Phythian-Adams; Elisabeth Wachter; Lauren Webb; Tara Sutherland; Graham D Thomas; John R Grainger; Jim Selfridge; Andrew N J McKenzie; Judith 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 Cook, Heather Owen, Aimée M Deaton, Jessica G Borger, Sheila Brown, Thomas Clouaire, Gareth-Rhys Jones, Lucy H Jones, Rachel J Lundie, Angela K Marley, Vicky L Morrison, Alexander Phythian-Adams, Elisabeth Wachter, Lauren Webb, Tara Sutherland, Graham D Thomas, John R Grainger, Jim Selfridge, Andrew N J McKenzie, Judith AllenSusanna C Fagerholm, Rick M Maizels, Alasdair C Ivens, Adrian Bird, Andrew S MacDonald

Medical Sciences

Research output: Contribution to journal › Article › peer-review

64 Citations (Scopus)

2 Downloads (Pure)

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

Bibliographical note

Acknowledgements
This work was supported by the M.R.C. (G0701437 to A.S.M.) and the Wellcome Trust, Cancer Research United Kingdom and the B.B.S.R.C (A.B., L.H.J., G-R.J., G.D.T., J.R.G., R.M.M., S.C.F. and V.L.M.). DNA sequencing was managed and performed at the Wellcome Trust Sanger Institute. Illumina BeadChip experiments were performed at the Wellcome Trust Clinical Research Facility, Edinburgh, by Louise Evenden and Lee Murphy. We thank Rinku Rajan for technical support; Yoshihide Kanaoka for advice on the HDM protocol; Martin Waterfall for cell sorting and assistance with flow cytometry; Mark Travis and John Worthington for supplying transforming growth factor-β; and David Gray, Caetano Reis e Sousa, Kevin Couper and Markus Mohrs for provision of IL-10eGFP, CD11cCre and KN2 mice. Schistosome life cycle stages used to generate eggs and SEA for this research were supplied by the N.I.A.I.D. Schistosomiasis Resource Center at the Biomedical Research Institute (Rockville, MD, USA) through Contract N01-AI-30026.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ncomms7920

Cook_etal_NC_A_Dominant_Role_VOR
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Final published version, 1.57 MBLicence: CC BY

Cite this

Cook, P., Owen, H., Deaton, A. M., Borger, J. G., Brown, S., Clouaire, T., Jones, G.-R., Jones, L. H., Lundie, R. J., Marley, A. K., Morrison, V. L., Phythian-Adams, A., Wachter, E., Webb, L., Sutherland, T., 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

Cook, P, Owen, H, Deaton, AM, Borger, JG, Brown, S, Clouaire, T, Jones, G-R, Jones, LH, Lundie, RJ, Marley, AK, Morrison, VL, Phythian-Adams, A, Wachter, E, Webb, L, Sutherland, T, Thomas, GD, Grainger, JR, Selfridge, J, McKenzie, ANJ, Allen, J, 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

@article{2f7e70554e974572992a88f679c9d520,

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 = "Peter Cook and Heather Owen and Deaton, {Aim{\'e}e M} and Borger, {Jessica G} and Sheila Brown and Thomas Clouaire and Gareth-Rhys Jones and Jones, {Lucy H} and Lundie, {Rachel J} and Marley, {Angela K} and Morrison, {Vicky L} and Alexander Phythian-Adams and Elisabeth Wachter and Lauren Webb and Tara Sutherland and Thomas, {Graham D} and Grainger, {John R} and Jim Selfridge and McKenzie, {Andrew N J} and Judith Allen and Fagerholm, {Susanna C} and Maizels, {Rick M} and Ivens, {Alasdair C} and Adrian Bird and MacDonald, {Andrew S}",

note = "Acknowledgements This work was supported by the M.R.C. (G0701437 to A.S.M.) and the Wellcome Trust, Cancer Research United Kingdom and the B.B.S.R.C (A.B., L.H.J., G-R.J., G.D.T., J.R.G., R.M.M., S.C.F. and V.L.M.). DNA sequencing was managed and performed at the Wellcome Trust Sanger Institute. Illumina BeadChip experiments were performed at the Wellcome Trust Clinical Research Facility, Edinburgh, by Louise Evenden and Lee Murphy. We thank Rinku Rajan for technical support; Yoshihide Kanaoka for advice on the HDM protocol; Martin Waterfall for cell sorting and assistance with flow cytometry; Mark Travis and John Worthington for supplying transforming growth factor-β; and David Gray, Caetano Reis e Sousa, Kevin Couper and Markus Mohrs for provision of IL-10eGFP, CD11cCre and KN2 mice. Schistosome life cycle stages used to generate eggs and SEA for this research were supplied by the N.I.A.I.D. Schistosomiasis Resource Center at the Biomedical Research Institute (Rockville, MD, USA) through Contract N01-AI-30026.",

year = "2015",

month = apr,

day = "24",

doi = "10.1038/ncomms7920",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

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

AU - Cook, Peter

AU - Owen, Heather

AU - Deaton, Aimée M

AU - Borger, Jessica G

AU - Brown, Sheila

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

AU - Wachter, Elisabeth

AU - Webb, Lauren

AU - Sutherland, Tara

AU - Thomas, Graham D

AU - Grainger, John R

AU - Selfridge, Jim

AU - McKenzie, Andrew N J

AU - Allen, Judith

AU - Fagerholm, Susanna C

AU - Maizels, Rick M

AU - Ivens, Alasdair C

AU - Bird, Adrian

AU - MacDonald, Andrew S

N1 - Acknowledgements This work was supported by the M.R.C. (G0701437 to A.S.M.) and the Wellcome Trust, Cancer Research United Kingdom and the B.B.S.R.C (A.B., L.H.J., G-R.J., G.D.T., J.R.G., R.M.M., S.C.F. and V.L.M.). DNA sequencing was managed and performed at the Wellcome Trust Sanger Institute. Illumina BeadChip experiments were performed at the Wellcome Trust Clinical Research Facility, Edinburgh, by Louise Evenden and Lee Murphy. We thank Rinku Rajan for technical support; Yoshihide Kanaoka for advice on the HDM protocol; Martin Waterfall for cell sorting and assistance with flow cytometry; Mark Travis and John Worthington for supplying transforming growth factor-β; and David Gray, Caetano Reis e Sousa, Kevin Couper and Markus Mohrs for provision of IL-10eGFP, CD11cCre and KN2 mice. Schistosome life cycle stages used to generate eggs and SEA for this research were supplied by the N.I.A.I.D. Schistosomiasis Resource Center at the Biomedical Research Institute (Rockville, MD, USA) through Contract N01-AI-30026.

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.

U2 - 10.1038/ncomms7920

DO - 10.1038/ncomms7920

M3 - Article

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.

Abstract

Bibliographical note

UN SDGs

Access to Document

Fingerprint

Cite this