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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.

DOI:10.3389/fimmu.2023.1137538
PMID:37359530
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10288978/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/7e052b90638d/fimmu-14-1137538-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/7d615379c1ec/fimmu-14-1137538-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/f45ce4ad917f/fimmu-14-1137538-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/afa12f186926/fimmu-14-1137538-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/aaf6d2c06f85/fimmu-14-1137538-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/4d7336a92919/fimmu-14-1137538-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/731320d2d83d/fimmu-14-1137538-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/7e052b90638d/fimmu-14-1137538-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/7d615379c1ec/fimmu-14-1137538-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/f45ce4ad917f/fimmu-14-1137538-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/afa12f186926/fimmu-14-1137538-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/aaf6d2c06f85/fimmu-14-1137538-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/4d7336a92919/fimmu-14-1137538-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/731320d2d83d/fimmu-14-1137538-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c4/10288978/7e052b90638d/fimmu-14-1137538-g007.jpg

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