载有维生素 D3 的脂质体诱导人树突状细胞中的调节回路。
Liposomes loaded with vitamin D3 induce regulatory circuits in human dendritic cells.
机构信息
Amsterdam Universitair Medische Centra (UMC), Department of Experimental Immunology, Amsterdam Institute for Infection & Immunity, University of Amsterdam, Amsterdam, Netherlands.
Division of BioTherapeutics, Leiden Academic Center for Drug Research, Leiden, Netherlands.
出版信息
Front Immunol. 2023 Jun 9;14:1137538. doi: 10.3389/fimmu.2023.1137538. eCollection 2023.
INTRODUCTION
Nanomedicine provides a promising platform for manipulating dendritic cells (DCs) and the ensuing adaptive immune response. For the induction of regulatory responses, DCs can be targeted with nanoparticles incorporating tolerogenic adjuvants and auto-antigens or allergens.
METHODS
Here, we investigated the tolerogenic effect of different liposome formulations loaded with vitamin D3 (VD3). We extensively phenotyped monocyte-derived DCs (moDCs) and skin DCs and assessed DC-induced regulatory CD4+ T cells in coculture.
RESULTS
Liposomal VD3 primed-moDCs induced the development of regulatory CD4+ T cells (Tregs) that inhibited bystander memory T cell proliferation. Induced Tregs were of the FoxP3+ CD127low phenotype, also expressing TIGIT. Additionally, liposome-VD3 primed moDCs inhibited the development of T helper 1 (Th1) and T helper 17 (Th17) cells. Skin injection of VD3 liposomes selectively stimulated the migration of CD14+ skin DCs.
DISCUSSION
These results suggest that nanoparticulate VD3 is a tolerogenic tool for DC-mediated induction of regulatory T cell responses.
简介
纳米医学为操纵树突状细胞（DC）及其随后的适应性免疫反应提供了一个有前途的平台。为了诱导调节性反应，可以用负载耐受原性佐剂和自身抗原或过敏原的纳米颗粒靶向 DC。
方法
在这里，我们研究了负载维生素 D3（VD3）的不同脂质体配方的耐受原性效应。我们广泛表型分析了单核细胞来源的树突状细胞（moDCs）和皮肤树突状细胞，并在共培养中评估了 DC 诱导的调节性 CD4+T 细胞。
结果
脂质体 VD3 引发的 moDC 诱导了调节性 CD4+T 细胞（Tregs）的发育，抑制了旁观者记忆 T 细胞的增殖。诱导的 Tregs 具有 FoxP3+CD127low 表型，也表达 TIGIT。此外，脂质体 VD3 引发的 moDC 抑制了辅助性 T 细胞 1（Th1）和辅助性 T 细胞 17（Th17）细胞的发育。VD3 脂质体的皮肤注射选择性地刺激了 CD14+皮肤 DC 的迁移。
讨论
这些结果表明，纳米颗粒 VD3 是一种用于 DC 介导的调节性 T 细胞反应诱导的耐受原性工具。
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