Vitamin D3 Priming of Dendritic Cells Shifts Human Neutrophil-Dependent Th17 Cell Development to Regulatory T Cells.

Autor: Hafkamp FMJ; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands., Taanman-Kueter EWM; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands., van Capel TMM; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands., Kormelink TG; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands., de Jong EC; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2022 Jul 07; Vol. 13, pp. 872665. Date of Electronic Publication: 2022 Jul 07 (Print Publication: 2022).
DOI: 10.3389/fimmu.2022.872665
Abstrakt: Vitamin D3 (VD3) is a potential adjuvant for use in tolerogenic vaccine formulations that target dendritic cells (DCs) for the treatment of chronic inflammatory disorders, e.g., autoimmune diseases. These disorders are often associated with enhanced activity of IL-17-producing T helper 17 (Th17) cells which develop in a DC-driven and neutrophil-dependent fashion. Here, we investigated the effect of VD3 on Candida albicans -specific human T-cell differentiation, since C. albicans is a model pathogen for Th17 cell development. VD3 priming of DCs restricted neutrophil-dependent Th17 cell development and neutrophil-independent Th1 cell formation from naive CD4 + T cells. In line with this, the production of Th1/Th17-polarizing cytokines IL-12 and IL-23 by DCs was reduced by VD3 priming. Development of both FoxP3 + CD127 low CD25 + Tregs and IL-10-producing T cells was significantly enhanced in VD3-primed conditions, even in the presence of neutrophils. ICOS + Tregs, major IL-10 producers, CD69 + FoxP3 + , and TIGIT + FoxP3 + Tregs were significantly induced by VD3 priming as well. Our data support the potential use of VD3 as an adjuvant to induce tolerance in the treatment of autoimmune disorders, including those in which neutrophils are involved in pathogenesis, since we show that Treg development is enhanced by VD3 even in the presence of neutrophils, while Th17 cell development is restricted.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Hafkamp, Taanman-Kueter, van Capel, Kormelink and de Jong.)
Databáze: MEDLINE
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