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Front Immunol. 2017 Oct 30;8:1429. doi: 10.3389/fimmu.2017.01429. eCollection 2017.

Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A Signaling.

Author information

1
Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, Netherlands.
2
Faculty of Medicine, Department of Parasitology, Universitas Indonesia, Jakarta, Indonesia.

Abstract

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.

KEYWORDS:

G-coupled protein receptor 109A; butyrate; dendritic cells; histone deacetylases; retinaldehyde dehydrogenase; retinoic acid; short-chain fatty acids; type 1 regulatory T cells

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