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

卷:8

Bart Everts¹  Maria Yazdanbakhsh¹  Leonard R. Pelgrom¹  Alwin J. van der Ham¹  Maria M. M. Kaisar² 

[1] Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, Netherlands;

[2] Faculty of Medicine, Department of Parasitology, Universitas Indonesia, Jakarta, Indonesia;

关键词: short-chain fatty acids;    butyrate;    dendritic cells;    type 1 regulatory T cells;    histone deacetylases;    G-coupled protein receptor 109A;   

DOI  :  10.3389/fimmu.2017.01429

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown