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

Sander de Kivit; Atanaska I Kostadinova; JoAnn Kerperien; Veronica Ayechu Muruzabal; Mary E Morgan; Leon M J Knippels; Aletta D Kraneveld; Johan Garssen; Linette E M Willemsen

doi:10.1159/000479817

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

Sander de Kivit^*, Atanaska I Kostadinova, JoAnn Kerperien, Veronica Ayechu Muruzabal, Mary E Morgan, Leon M J Knippels, Aletta D Kraneveld, Johan Garssen, Linette E M Willemsen

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Intestinal epithelial cells (IEC) drive regulatory T cell (Treg) 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.

Original language	English
Pages (from-to)	609-620
Number of pages	12
Journal	Journal of Innate Immunity
Volume	9
Issue number	6
DOIs	https://doi.org/10.1159/000479817
Publication status	Published - Nov 2017

Keywords

dendritic cells
Intestinal epithelial cells
galectin 9
Toll-like receptor 9

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479817Final published version, 450 KBLicence: CC BY-NC-ND

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de Kivit, S., Kostadinova, A. I., Kerperien, J., Ayechu Muruzabal, V., Morgan, M. E., Knippels, L. M. J., Kraneveld, A. D., Garssen, J., & Willemsen, L. E. M. (2017). Galectin-9 Produced by Intestinal Epithelial Cells Enhances Aldehyde Dehydrogenase Activity in Dendritic Cells in a PI3K- and p38-Dependent Manner. Journal of Innate Immunity, 9(6), 609-620. https://doi.org/10.1159/000479817

@article{d6bc8293b6914f478a1b5fb0f1703844,

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

abstract = "Intestinal epithelial cells (IEC) drive regulatory T cell (Treg) 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.",

keywords = "dendritic cells, Intestinal epithelial cells, galectin 9, Toll-like receptor 9",

author = "{de Kivit}, Sander and Kostadinova, {Atanaska I} and JoAnn Kerperien and {Ayechu Muruzabal}, Veronica and Morgan, {Mary E} and Knippels, {Leon M J} and Kraneveld, {Aletta D} and Johan Garssen and Willemsen, {Linette E M}",

note = "{\textcopyright} 2017 S. Karger AG, Basel.",

year = "2017",

month = nov,

doi = "10.1159/000479817",

language = "English",

volume = "9",

pages = "609--620",

journal = "Journal of Innate Immunity",

issn = "1662-811X",

publisher = "S. Karger AG",

number = "6",

}

de Kivit, S, Kostadinova, AI, Kerperien, J, Ayechu Muruzabal, V, Morgan, ME, Knippels, LMJ, Kraneveld, AD , Garssen, J & Willemsen, LEM 2017, 'Galectin-9 Produced by Intestinal Epithelial Cells Enhances Aldehyde Dehydrogenase Activity in Dendritic Cells in a PI3K- and p38-Dependent Manner', Journal of Innate Immunity, vol. 9, no. 6, pp. 609-620. https://doi.org/10.1159/000479817

TY - JOUR

T1 - Galectin-9 Produced by Intestinal Epithelial Cells Enhances Aldehyde Dehydrogenase Activity in Dendritic Cells in a PI3K- and p38-Dependent Manner

AU - de Kivit, Sander

AU - Kostadinova, Atanaska I

AU - Kerperien, JoAnn

AU - Ayechu Muruzabal, Veronica

AU - Morgan, Mary E

AU - Knippels, Leon M J

AU - Kraneveld, Aletta D

AU - Garssen, Johan

AU - Willemsen, Linette E M

PY - 2017/11

Y1 - 2017/11

N2 - Intestinal epithelial cells (IEC) drive regulatory T cell (Treg) 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.

AB - Intestinal epithelial cells (IEC) drive regulatory T cell (Treg) 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.

KW - dendritic cells

KW - Intestinal epithelial cells

KW - galectin 9

KW - Toll-like receptor 9

U2 - 10.1159/000479817

DO - 10.1159/000479817

M3 - Article

C2 - 28889122

SN - 1662-811X

VL - 9

SP - 609

EP - 620

JO - Journal of Innate Immunity

JF - Journal of Innate Immunity

IS - 6

ER -

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

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Keywords

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