Galectin-9 Produced by Intestinal Epithelial Cells Enhances Aldehyde Dehydrogenase Activity in Dendritic Cells in a PI3K-and p38-Dependent Manner

被引：17
作者：
de Kivit, Sander [1 ]
Kostadinova, Atanaska I. [1 ]
Kerperien, Joann [1 ]
Muruzabal, Veronica Ayechu [1 ]
Morgan, Mary E. [1 ]
Knippels, Leon M. J. [1 ,2 ]
Kraneveld, Aletta D. [1 ]
Garssen, Johan [1 ,2 ]
Willemsen, Linette E. M. [1 ]
机构：
[1] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Div Pharmacol, POB 80082, NL-3508 TB Utrecht, Netherlands
[2] Danone Nutricia Res, Utrecht, Netherlands
来源：
JOURNAL OF INNATE IMMUNITY | 2017年 / 9卷 / 06期
关键词：
Dendritic cells; Intestinal epithelial cells; Galectin-9; Toll-like receptor 9; REGULATORY T-CELLS; MOUSE BONE-MARROW; RETINOIC-ACID; GM-CSF; IMMUNE HOMEOSTASIS; REG-CELLS; INFLAMMATION; GENERATION; EXPRESSION; RESPONSES;
D O I：
10.1159/000479817
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Intestinal epithelial cells (IEC) drive regulatory T cell (T-reg) responses by promoting the differentiation of aldehyde dehydrogenase (ALDH)-expressing CD103(+) dendritic cells (DC). Apical stimulation of TLR9 by CpG DNA on IEC supports galectin-9 expression by IEC, which is promoted by short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (GF). While galectin-9 can induce the maturation of monocyte-derived DC (moDC), the contribution of galectin-9 on the induction of ALDH activity in DC is not known. To this end, DC were stimulated with galectin-9, and ALDH activity and the expression of CD103 were assessed. ALDH activity was increased by moDC exposed to galectin-9, while the expression of CD103 remained unaltered. Galectin-9 secreted by IEC apically exposed to CpG DNA and GF enhanced ALDH activity, but not CD103 expression by moDC, which was abrogated upon galectin-9 neutralization. Similar observations were found in murine GM-CSF-cultured bone marrow-derived DC (BMDC). Using Flt3L-cultured BMDC and ex vivo murine splenic DC, it was observed that galectin-9 only enhanced ALDH activity in the presence of GM-CSF in CD103 cells. The induction of ALDH activity in BMDC was dependent on p38 and PI3K signaling. These data indicate a novel role for galectin-9 in modulating innate immunity by inducing ALDH activity in DC. (C) 2017 S. Karger AG, Basel.
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收藏
页码：609 / 620
页数：12
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