{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:45:39Z","timestamp":1788777939073,"version":"build-2803163510"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013derived DCs to Zn in vitro induced a tolerogenic phenotype by diminishing surface MHC class II (MHCII) and promoting the tolerogenic markers, programmed death\u2013ligand (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\u2013Th17 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1600410","type":"journal-article","created":{"date-parts":[[2016,7,27]],"date-time":"2016-07-27T22:38:59Z","timestamp":1469659139000},"page":"1864-1876","source":"Crossref","is-referenced-by-count":74,"title":["Zinc Induces Dendritic Cell Tolerogenic Phenotype and Skews Regulatory T Cell\u2013Th17 Balance"],"prefix":"10.1093","volume":"197","author":[{"given":"Mariam Mathew","family":"George","sequence":"first","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavitha","family":"Subramanian Vignesh","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, College of Medicine, University of Cincinnati , Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio A","family":"Landero Figueroa","sequence":"additional","affiliation":[{"name":"University of Cincinnati\/Agilent Technologies Metallomics Center of the Americas, Department of Chemistry, University of Cincinnati , Cincinnati, OH 45221"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A","family":"Caruso","sequence":"additional","affiliation":[{"name":"University of Cincinnati\/Agilent Technologies Metallomics Center of the Americas, Department of Chemistry, University of Cincinnati , Cincinnati, OH 45221"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"George S","family":"Deepe","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, College of Medicine, University of Cincinnati , Cincinnati, OH 45267"},{"name":"Veterans Affairs Hospital , Cincinnati, OH 45220"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,9,1]]},"reference":[{"key":"2025030617475968600_r1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nri1996","article-title":"Steady-state and inflammatory dendritic-cell development","volume":"7","author":"Shortman","year":"2007","journal-title":"Nat. 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