Literature DB >> 29100619

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

Sakhila Ghimire1, Carina Matos1, Massimiliano Caioni1, Daniela Weber1, Katrin Peter1, Ernst Holler1, Marina Kreutz1, Kathrin Renner2.   

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.
Copyright © 2017 Elsevier GmbH. All rights reserved.

Entities:  

Keywords:  IFNɣ; IL-12; Indoxyl 3-sulfate; T cells; TNF; Tolerogenic dendritic cells

Mesh:

Substances:

Year:  2017        PMID: 29100619     DOI: 10.1016/j.imbio.2017.10.014

Source DB:  PubMed          Journal:  Immunobiology        ISSN: 0171-2985            Impact factor:   3.144


  9 in total

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