Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.
Front Immunol. 2022 Jul 7;13:872665. doi: 10.3389/fimmu.2022.872665. eCollection 2022.
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 -specific human T-cell differentiation, since 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 FoxP3CD127CD25 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, CD69FoxP3, and TIGITFoxP3 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.
维生素 D3（VD3）是一种有潜力的佐剂，可用于针对树突状细胞（DC）的耐受原性疫苗配方，以治疗慢性炎症性疾病，例如自身免疫性疾病。这些疾病通常与产生白细胞介素-17（IL-17）的辅助性 T 细胞 17（Th17）细胞的活性增强有关，而 Th17 细胞的发展是在 DC 驱动和中性粒细胞依赖的方式下发生的。在这里，我们研究了 VD3 对 -特异性人 T 细胞分化的影响，因为 是 Th17 细胞发展的模型病原体。VD3 对 DC 的初免限制了中性粒细胞依赖的 Th17 细胞的发育和来自幼稚 CD4 T 细胞的中性粒细胞非依赖的 Th1 细胞的形成。与此一致的是，VD3 初免降低了 DC 产生 Th1/Th17 极化细胞因子 IL-12 和 IL-23 的能力。在 VD3 初免条件下，FoxP3CD127CD25 Treg 和产生 IL-10 的 T 细胞的发育均显著增强，即使存在中性粒细胞也是如此。ICOS Treg、主要的 IL-10 产生者、CD69FoxP3 和 TIGITFoxP3 Treg 也被 VD3 初免显著诱导。我们的数据支持将 VD3 用作佐剂来诱导自身免疫性疾病的耐受的潜力，包括那些涉及中性粒细胞参与发病机制的疾病，因为我们表明，即使存在中性粒细胞，VD3 也能增强 Treg 的发育，而限制 Th17 细胞的发育。
