Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter

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Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter. / Hill, Elaine V; Ng, T H Sky; Burton, Bronwen R; Oakley, Charly M; Malik, Karim; Wraith, David C; Wraith, David.

In: European Journal of Immunology, Vol. 45, No. 4, 04.2015, p. 1103-15.

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Hill, Elaine V ; Ng, T H Sky ; Burton, Bronwen R ; Oakley, Charly M ; Malik, Karim ; Wraith, David C ; Wraith, David. / Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter. In: European Journal of Immunology. 2015 ; Vol. 45, No. 4. pp. 1103-15.

Bibtex

@article{4c8bddd3d95049a29cab8c78f79325af,
title = "Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter",
abstract = "The serine/threonine kinase glycogen synthase kinase-3 (GSK3) plays an important role in balancing pro- and anti-inflammatory cytokines. We have examined the role of GSK3 in production of IL-10 by subsets of CD4(+) T helper cells. Treatment of naive murine CD4(+) T cells with GSK3 inhibitors did not affect their production of IL-10. However, treatment of Th1 and Th2 cells with GSK3 inhibitors dramatically increased production of IL-10. GSK3 inhibition also led to upregulation of IL-10 among Th1, Th2, and Th17 subsets isolated from human blood. The encephalitogenic potential of GSK3 inhibitor treated murine Th1 cells was significantly reduced in adoptive transfer experiments by an IL-10-dependent mechanism. Analysis of the murine IL-10 promoter in response to inhibition of GSK3 in Th1 cells showed modification to a transcriptionally active state indicated by changes in histone H3 acetylation and methylation. Additionally, GSK3 inhibition increased expression of the transcription factors c-Maf, Nfil3, and GATA3, correlating with the increase in IL-10. These findings are important in the context of autoimmune disease since they show that it is possible to reprogram disease-causing cells through GSK3 inhibition.",
keywords = "Acetylation, Adoptive Transfer, Animals, Basic-Leucine Zipper Transcription Factors, Cells, Cultured, Dendritic Cells, Encephalomyelitis, Autoimmune, Experimental, GATA3 Transcription Factor, Glycogen Synthase Kinase 3, Histones, Humans, Inflammation, Interleukin-10, Methylation, Mice, Mice, Knockout, Promoter Regions, Genetic, Proto-Oncogene Proteins c-maf, Th1 Cells, Th17 Cells, Th2 Cells, Journal Article, Research Support, Non-U.S. Gov't",
author = "Hill, {Elaine V} and Ng, {T H Sky} and Burton, {Bronwen R} and Oakley, {Charly M} and Karim Malik and Wraith, {David C} and David Wraith",
note = "{\textcopyright} 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2015",
month = apr,
doi = "10.1002/eji.201444661",
language = "English",
volume = "45",
pages = "1103--15",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "4",

}

RIS

TY - JOUR

T1 - Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter

AU - Hill, Elaine V

AU - Ng, T H Sky

AU - Burton, Bronwen R

AU - Oakley, Charly M

AU - Malik, Karim

AU - Wraith, David C

AU - Wraith, David

N1 - © 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2015/4

Y1 - 2015/4

N2 - The serine/threonine kinase glycogen synthase kinase-3 (GSK3) plays an important role in balancing pro- and anti-inflammatory cytokines. We have examined the role of GSK3 in production of IL-10 by subsets of CD4(+) T helper cells. Treatment of naive murine CD4(+) T cells with GSK3 inhibitors did not affect their production of IL-10. However, treatment of Th1 and Th2 cells with GSK3 inhibitors dramatically increased production of IL-10. GSK3 inhibition also led to upregulation of IL-10 among Th1, Th2, and Th17 subsets isolated from human blood. The encephalitogenic potential of GSK3 inhibitor treated murine Th1 cells was significantly reduced in adoptive transfer experiments by an IL-10-dependent mechanism. Analysis of the murine IL-10 promoter in response to inhibition of GSK3 in Th1 cells showed modification to a transcriptionally active state indicated by changes in histone H3 acetylation and methylation. Additionally, GSK3 inhibition increased expression of the transcription factors c-Maf, Nfil3, and GATA3, correlating with the increase in IL-10. These findings are important in the context of autoimmune disease since they show that it is possible to reprogram disease-causing cells through GSK3 inhibition.

AB - The serine/threonine kinase glycogen synthase kinase-3 (GSK3) plays an important role in balancing pro- and anti-inflammatory cytokines. We have examined the role of GSK3 in production of IL-10 by subsets of CD4(+) T helper cells. Treatment of naive murine CD4(+) T cells with GSK3 inhibitors did not affect their production of IL-10. However, treatment of Th1 and Th2 cells with GSK3 inhibitors dramatically increased production of IL-10. GSK3 inhibition also led to upregulation of IL-10 among Th1, Th2, and Th17 subsets isolated from human blood. The encephalitogenic potential of GSK3 inhibitor treated murine Th1 cells was significantly reduced in adoptive transfer experiments by an IL-10-dependent mechanism. Analysis of the murine IL-10 promoter in response to inhibition of GSK3 in Th1 cells showed modification to a transcriptionally active state indicated by changes in histone H3 acetylation and methylation. Additionally, GSK3 inhibition increased expression of the transcription factors c-Maf, Nfil3, and GATA3, correlating with the increase in IL-10. These findings are important in the context of autoimmune disease since they show that it is possible to reprogram disease-causing cells through GSK3 inhibition.

KW - Acetylation

KW - Adoptive Transfer

KW - Animals

KW - Basic-Leucine Zipper Transcription Factors

KW - Cells, Cultured

KW - Dendritic Cells

KW - Encephalomyelitis, Autoimmune, Experimental

KW - GATA3 Transcription Factor

KW - Glycogen Synthase Kinase 3

KW - Histones

KW - Humans

KW - Inflammation

KW - Interleukin-10

KW - Methylation

KW - Mice

KW - Mice, Knockout

KW - Promoter Regions, Genetic

KW - Proto-Oncogene Proteins c-maf

KW - Th1 Cells

KW - Th17 Cells

KW - Th2 Cells

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/eji.201444661

DO - 10.1002/eji.201444661

M3 - Article

C2 - 25627813

VL - 45

SP - 1103

EP - 1115

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 4

ER -