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J Immunol. 2016 Sep 1;197(5):1864-76. doi: 10.4049/jimmunol.1600410. Epub 2016 Jul 27.

Zinc Induces Dendritic Cell Tolerogenic Phenotype and Skews Regulatory T Cell-Th17 Balance.

Author information

1
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229;
2
Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, OH 45267;
3
University of Cincinnati/Agilent Technologies Metallomics Center of the Americas, Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221; and.
4
Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, OH 45267; Veterans Affairs Hospital, Cincinnati, OH 45220 george.deepe@uc.edu.

Abstract

Zinc (Zn) is an essential metal for development and maintenance of both the innate and adaptive compartments of the immune system. Zn homeostasis impacts maturation of dendritic cells (DCs) that are important in shaping T cell responses. The mechanisms by which Zn regulates the tolerogenic phenotype of DCs remain largely unknown. In this study, we investigated the effect of Zn on DC phenotype and the generation of Foxp3(+) regulatory T cells (Tregs) using a model of Histoplasma capsulatum fungal infection. Exposure of bone marrow-derived DCs to Zn in vitro induced a tolerogenic phenotype by diminishing surface MHC class II (MHCII) and promoting the tolerogenic markers, programmed death-ligand (PD-L)1, PD-L2, and the tryptophan degrading enzyme, IDO. Zn triggered tryptophan degradation by IDO and kynurenine production by DCs and strongly suppressed the proinflammatory response to stimulation by TLR ligands. In vivo, Zn supplementation and subsequent H. capsulatum infection supressed MHCII on DCs, enhanced PD-L1 and PD-L2 expression on MHCII(lo) DCs, and skewed the Treg-Th17 balance in favor of Foxp3(+) Tregs while decreasing Th17 cells. Thus, Zn shapes the tolerogenic potential of DCs in vitro and in vivo and promotes Tregs during fungal infection.

PMID:
27465530
PMCID:
PMC4992588
DOI:
10.4049/jimmunol.1600410
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflicts of interest.

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