Zinc induces dendritic cell tolerogenic phenotype and skews regulatory T Cell-Th17 balance

Mariam Mathew George, Kavitha Subramanian Vignesh, Julio A. Landero Figueroa, Joseph A. Caruso, George S. Deepe

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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 MHCIIlo 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.

Original languageEnglish
Pages (from-to)1864-1876
Number of pages13
JournalJournal of Immunology
Volume197
Issue number5
DOIs
StatePublished - 1 Sep 2016
Externally publishedYes

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