Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A Signaling
Recently, it has become clear that short-chain fatty acids (SCFAs), and in particular butyrate, have anti-inflammatory properties. Murine studies have shown that butyrate can promote regulatory T cells via the induction of tolerogenic dendritic cells (DCs). However, the effects of SCFAs on human DCs...
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doaj-412e4d2e65254e29bec8ddec6ac5f0042020-11-24T23:13:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01429299468Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A SignalingMaria M. M. Kaisar0Maria M. M. Kaisar1Leonard R. Pelgrom2Alwin J. van der Ham3Maria Yazdanbakhsh4Bart Everts5Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, NetherlandsFaculty of Medicine, Department of Parasitology, Universitas Indonesia, Jakarta, IndonesiaDepartment of Parasitology, Leiden University Medical Center (LUMC), Leiden, NetherlandsDepartment of Parasitology, Leiden University Medical Center (LUMC), Leiden, NetherlandsDepartment of Parasitology, Leiden University Medical Center (LUMC), Leiden, NetherlandsDepartment of Parasitology, Leiden University Medical Center (LUMC), Leiden, NetherlandsRecently, it has become clear that short-chain fatty acids (SCFAs), and in particular butyrate, have anti-inflammatory properties. Murine studies have shown that butyrate can promote regulatory T cells via the induction of tolerogenic dendritic cells (DCs). However, the effects of SCFAs on human DCs and how they affect their capacity to prime and polarize T-cell responses have not been addressed. Here, we report that butyrate suppresses LPS-induced maturation and metabolic reprogramming of human monocyte-derived DCs (moDCs) and conditions them to polarize naive CD4+ T cells toward IL-10-producing type 1 regulatory T cells (Tr1). This effect was dependent on induction of the retinoic acid-producing enzyme retinaldehyde dehydrogenase 1 in DCs. The induction of retinaldehyde dehydrogenase activity and Tr1 cell differentiation by butyrate was dependent on simultaneous inhibition of histone deacetylases and signaling through G protein-coupled receptor 109A. Taken together, we reveal that butyrate is a potent inducer of tolerogenic human DCs, thereby shedding new light on the cellular and molecular mechanisms through which SCFAs can exert their immunomodulatory effects in humans.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01429/fullshort-chain fatty acidsbutyratedendritic cellstype 1 regulatory T cellshistone deacetylasesG-coupled protein receptor 109A |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria M. M. Kaisar Maria M. M. Kaisar Leonard R. Pelgrom Alwin J. van der Ham Maria Yazdanbakhsh Bart Everts |
spellingShingle |
Maria M. M. Kaisar Maria M. M. Kaisar Leonard R. Pelgrom Alwin J. van der Ham Maria Yazdanbakhsh Bart Everts Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A Signaling Frontiers in Immunology short-chain fatty acids butyrate dendritic cells type 1 regulatory T cells histone deacetylases G-coupled protein receptor 109A |
author_facet |
Maria M. M. Kaisar Maria M. M. Kaisar Leonard R. Pelgrom Alwin J. van der Ham Maria Yazdanbakhsh Bart Everts |
author_sort |
Maria M. M. Kaisar |
title |
Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A Signaling |
title_short |
Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A Signaling |
title_full |
Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A Signaling |
title_fullStr |
Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A Signaling |
title_full_unstemmed |
Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A Signaling |
title_sort |
butyrate conditions human dendritic cells to prime type 1 regulatory t cells via both histone deacetylase inhibition and g protein-coupled receptor 109a signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-10-01 |
description |
Recently, it has become clear that short-chain fatty acids (SCFAs), and in particular butyrate, have anti-inflammatory properties. Murine studies have shown that butyrate can promote regulatory T cells via the induction of tolerogenic dendritic cells (DCs). However, the effects of SCFAs on human DCs and how they affect their capacity to prime and polarize T-cell responses have not been addressed. Here, we report that butyrate suppresses LPS-induced maturation and metabolic reprogramming of human monocyte-derived DCs (moDCs) and conditions them to polarize naive CD4+ T cells toward IL-10-producing type 1 regulatory T cells (Tr1). This effect was dependent on induction of the retinoic acid-producing enzyme retinaldehyde dehydrogenase 1 in DCs. The induction of retinaldehyde dehydrogenase activity and Tr1 cell differentiation by butyrate was dependent on simultaneous inhibition of histone deacetylases and signaling through G protein-coupled receptor 109A. Taken together, we reveal that butyrate is a potent inducer of tolerogenic human DCs, thereby shedding new light on the cellular and molecular mechanisms through which SCFAs can exert their immunomodulatory effects in humans. |
topic |
short-chain fatty acids butyrate dendritic cells type 1 regulatory T cells histone deacetylases G-coupled protein receptor 109A |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01429/full |
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