Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection

We have previously demonstrated that weekly treatment of female prediabetic NOD mice with a low dose of the histone deacetylase inhibitor Trichostatin A (TSA) bestowed long-lasting, irreversible protection against autoimmune diabetes. Herein we show that drug treatment diminished the infiltration of...

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Autores principales:	Arathi Jayaraman, Maria Arianas, Sundararajan Jayaraman
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Epigenetics Genes Histone deacetylases Lymphocytes Macrophages Trichostatin A Biochemistry QD415-436 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/ec53d9afbdb04bc192e01f7d80954d02
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spelling	oai:doaj.org-article:ec53d9afbdb04bc192e01f7d80954d022021-11-22T04:33:26ZEpigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection2667-160310.1016/j.bbadva.2021.100031https://doaj.org/article/ec53d9afbdb04bc192e01f7d80954d022021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2667160321000302https://doaj.org/toc/2667-1603We have previously demonstrated that weekly treatment of female prediabetic NOD mice with a low dose of the histone deacetylase inhibitor Trichostatin A (TSA) bestowed long-lasting, irreversible protection against autoimmune diabetes. Herein we show that drug treatment diminished the infiltration of the pancreas with CD4+, CD8+ T cells, and Ly-6C+ monocytes. Significantly, TSA administration selectively repressed the expression of a set of genes exaggerated during diabetes and constitutively expressed primarily in the spleen and rarely in the pancreas. These genes encode lymphokines, macrophage-associated determinants, and transcription factors. Although the copy numbers of many histone deacetylases increased during diabetes in the spleen and pancreas, only those upregulated in the spleen were rendered sensitive to repression by TSA treatment. Mitogen-activated T lymphocytes derived from drug-treated donors displayed diminished diabetogenic potential following transfer into immunodeficient NOD.scid mice. In the immunocompromised recipients, diabetes caused by the transfer of activated T lymphocytes from untreated diabetic mice was hampered by the co-transfer of highly purified splenic CD11b+Ly-6C+ macrophages from drug-treated mice. However, the transfer of CD11b+Ly-6C+ macrophages from drug-treated mice failed to block ongoing diabetes in wild-type NOD mice. These data demonstrate that the modified gene expression and functional alteration of T lymphocytes and macrophages collectively contribute to diabetes protection afforded by the histone modifier in female NOD mice.Arathi JayaramanMaria ArianasSundararajan JayaramanElsevierarticleEpigeneticsGenesHistone deacetylasesLymphocytesMacrophagesTrichostatin ABiochemistryQD415-436GeneticsQH426-470ENBBA Advances, Vol 1, Iss , Pp 100031- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Epigenetics Genes Histone deacetylases Lymphocytes Macrophages Trichostatin A Biochemistry QD415-436 Genetics QH426-470
spellingShingle	Epigenetics Genes Histone deacetylases Lymphocytes Macrophages Trichostatin A Biochemistry QD415-436 Genetics QH426-470 Arathi Jayaraman Maria Arianas Sundararajan Jayaraman Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection
description	We have previously demonstrated that weekly treatment of female prediabetic NOD mice with a low dose of the histone deacetylase inhibitor Trichostatin A (TSA) bestowed long-lasting, irreversible protection against autoimmune diabetes. Herein we show that drug treatment diminished the infiltration of the pancreas with CD4+, CD8+ T cells, and Ly-6C+ monocytes. Significantly, TSA administration selectively repressed the expression of a set of genes exaggerated during diabetes and constitutively expressed primarily in the spleen and rarely in the pancreas. These genes encode lymphokines, macrophage-associated determinants, and transcription factors. Although the copy numbers of many histone deacetylases increased during diabetes in the spleen and pancreas, only those upregulated in the spleen were rendered sensitive to repression by TSA treatment. Mitogen-activated T lymphocytes derived from drug-treated donors displayed diminished diabetogenic potential following transfer into immunodeficient NOD.scid mice. In the immunocompromised recipients, diabetes caused by the transfer of activated T lymphocytes from untreated diabetic mice was hampered by the co-transfer of highly purified splenic CD11b+Ly-6C+ macrophages from drug-treated mice. However, the transfer of CD11b+Ly-6C+ macrophages from drug-treated mice failed to block ongoing diabetes in wild-type NOD mice. These data demonstrate that the modified gene expression and functional alteration of T lymphocytes and macrophages collectively contribute to diabetes protection afforded by the histone modifier in female NOD mice.
format	article
author	Arathi Jayaraman Maria Arianas Sundararajan Jayaraman
author_facet	Arathi Jayaraman Maria Arianas Sundararajan Jayaraman
author_sort	Arathi Jayaraman
title	Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection
title_short	Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection
title_full	Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection
title_fullStr	Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection
title_full_unstemmed	Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection
title_sort	epigenetic modulation of selected immune response genes and altered functions of t lymphocytes and macrophages collectively contribute to autoimmune diabetes protection
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/ec53d9afbdb04bc192e01f7d80954d02
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Epigenetic modulation of selected immune response genes and altered functions of T lymphocytes and macrophages collectively contribute to autoimmune diabetes protection

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