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

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

Bibliographic Details
Main Author: George, Mariam M., B.S.
Language:English
Published: University of Cincinnati / OhioLINK 2015
Subjects:
Immunology
Zinc
Tolerogenic
Dendritic Cell
regulatory T cell
Th17
Histoplasma
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439305564
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin14393055642021-08-03T06:32:47Z Zinc regulates tolerogenic dendritic cell phenotype and skews regulatory T cell- Th17 balance George, Mariam M., B.S. Immunology Zinc Tolerogenic Dendritic Cell regulatory T cell Th17 Histoplasma Zinc (Zn) is an essential metal for development and maintenance of both the innate and adaptive compartments the immune system. Regulation of Zn impacts maturation of dendritic cells (DCs) which are important in shaping T cell responses. The mechanisms by which Zn regulates phenotype of DCs and its impact on T cell differentiation are unknown. In this study, we sought to determine the effect of Zn on phenotype differentiation of DCs and the generation of forkhead box P3 (FOXP3+) regulatory T cells (Tregs) using a model of Histoplasma capsulatum fungal infection. Exposure of CD11c+ DCs to ZnSO4 in uninfected and H.capsulatum infected states in vitro decreased the surface expression of major histocompatibility complex (MHC) II and increased programmed death ligand (PDL)1, PDL2 and the tryptophan degrading enzyme, indoleamine 2,3 dioxygenase (IDO) that represent a tolerogenic phenotype. ZnSO4 robustly induced IDO enzymatic activity leading to tryptophan degradation and concomitant production of kyneurenine. ZnSO4 dampened the production of proinflammatory cytokines by DCs in response to stimulation of the toll like receptors (TLR)2, TLR3 and TLR4. In vivo treatment of H. capsulatum infected mice with 100µg ZnSO4/day induced a tolerogenic phenotype in DCs characterized by elevated expression of IDO. This phenotype was associated with an elevated proportion of FOXP3+ Tregs and decreased interleukin 17 (IL-17) producing Th17 cells. Thus, in vitro and in vivo, Zn shapes the tolerogenic potential of DCs and may induce naive T cell differentiation into a regulatory phenotype. Zn deficiency is associated with poor immune defences and autoimmunity. Our study reveals that the induction of tolerogenic DCs and Tregs by Zn supplementation can be potentially employed in immunosuppressive therapies such as in organ transplantation and to treat inflammation. Thus, manipulating Zn levels may serve as an attractive therapeutic strategy to alter specific functions of immune cells and promote tolerance or suppressive T cell immunity. 2015-09-11 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439305564 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439305564 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Immunology
Zinc
Tolerogenic
Dendritic Cell
regulatory T cell
Th17
Histoplasma
spellingShingle Immunology
Zinc
Tolerogenic
Dendritic Cell
regulatory T cell
Th17
Histoplasma
George, Mariam M., B.S.
Zinc regulates tolerogenic dendritic cell phenotype and skews regulatory T cell- Th17 balance
author George, Mariam M., B.S.
author_facet George, Mariam M., B.S.
author_sort George, Mariam M., B.S.
title Zinc regulates tolerogenic dendritic cell phenotype and skews regulatory T cell- Th17 balance
title_short Zinc regulates tolerogenic dendritic cell phenotype and skews regulatory T cell- Th17 balance
title_full Zinc regulates tolerogenic dendritic cell phenotype and skews regulatory T cell- Th17 balance
title_fullStr Zinc regulates tolerogenic dendritic cell phenotype and skews regulatory T cell- Th17 balance
title_full_unstemmed Zinc regulates tolerogenic dendritic cell phenotype and skews regulatory T cell- Th17 balance
title_sort zinc regulates tolerogenic dendritic cell phenotype and skews regulatory t cell- th17 balance
publisher University of Cincinnati / OhioLINK
publishDate 2015
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439305564
work_keys_str_mv AT georgemariammbs zincregulatestolerogenicdendriticcellphenotypeandskewsregulatorytcellth17balance
_version_ 1719438873426132992

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