Indoxyl 3-sulfate inhibits maturation and activation of human monocyte-derived dendritic cells

Ghimire, Sakhila and Matos, Carina and Caioni, Massimiliano and Weber, Daniela and Peter, Katrin and Holler, Ernst and Kreutz, Marina and Renner, Kathrin (2018) Indoxyl 3-sulfate inhibits maturation and activation of human monocyte-derived dendritic cells. IMMUNOBIOLOGY, 223 (2). pp. 239-245. ISSN 0171-2985,

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Abstract

Indole is produced from L-tryptophan by commensal bacteria and further metabolized to indoxyl 3-sulfate (I3S) in the liver. Physiologic concentrations of I3S are related to a lower risk to develop graft versus host disease in allogeneic stem cell transplanted patients pointing towards an immunoregulatory function of I3S. Here we investigated the impact of I3S on the maturation of human monocyte-derived dendritic cells (DCs). Even pathophysiologic concentrations of I3S did not affect viability of mature DCs, but I3S decreased the expression of co-stimulatory molecules such as CD80 and CD86 on mature DCs. Furthermore, I3S inhibited IL-12 and IL-6 secretion by mature DCs while IL-10 was significantly upregulated. Co-culture of I3S-treated mature DCs with allogeneic T cells revealed no alteration in T cell proliferation. However, interferon gamma and TNF production of T cells was suppressed. As I3S exerted no direct effect on T cells, the defect in T cell activation was mediated by I3S-treated mature DCs. Our study suggests an anti-inflammatory and tolerizing effect of I3S on human DCs.

Item Type: Article
Uncontrolled Keywords: ARYL-HYDROCARBON RECEPTOR; SULFATE; MICROBIOME; DIVERSITY; IL-12; Indoxyl 3-sulfate; Tolerogenic dendritic cells; IL-12; T cells; IFN gamma; TNF
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 20 Mar 2020 14:35
Last Modified: 20 Mar 2020 14:35
URI: https://pred.uni-regensburg.de/id/eprint/15166

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