Immunomodulatory effects of nanoparticles on dendritic cells in a model of allergic contact dermatitis: importance of PD-L2 expression.

Immunomodulatory effects of nanoparticles on dendritic cells in a model of allergic contact dermatitis: importance of PD-L2 expression.
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纳米颗粒对树突状细胞的免疫调节作用在过敏性接触性皮炎模型中:PD-L2表达的重要性。

DOI:
10.1038/s41598-023-42797-5
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发表时间:
2023-09-25
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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纳米颗粒(NP)皮肤暴露与变态反应性接触性皮炎的发病率增加有关。在我们之前使用小鼠接触超敏(CHS)模型的研究中,我们报告了二氧化硅20纳米(SiO_2)纳米颗粒抑制过敏反应,而掺入锰的二氧化钛纳米颗粒(MTiO_2)则加剧了过敏反应。在这项工作中,我们利用骨髓来源的树突状细胞(BMDCs)进行了体外实验,利用B7家族配体研究了有效的2,4-二硝基氟苯(DNFB)半抗原增敏剂与二氧化硅和纳米二氧化钛对BMDC的细胞毒性、细胞因子分泌和表型的联合作用。结果表明,DNFB和mTi02的行为相似,表现出促炎特性,而二氧化硅促进了幼稚的表型。我们观察到B7-H3(CD276)配体仅在CD80BMDCs(B7-1) + 上表达。过继转移CHS研究的结果,结合BMDC表型分析,指出PD-L2表达在调节获得性免疫反应中的重要性。这项工作确定了可用于预测NPs对接触性过敏的影响的指标,并指导基于细胞的治疗以诱导半抗原特异性免疫耐受的努力。
Nanoparticle (NP) skin exposure is linked to an increased prevalence of allergic contact dermatitis. In our prior studies using the mouse contact hypersensitivity (CHS) model, we reported that silica 20 nm (SiO2) NPs suppressed the allergic response and titanium dioxide NPs doped with manganese (mTiO2) exacerbated it. In this work, we conducted in vitro experiments using bone marrow-derived dendritic cells (BMDCs) to study the combinatorial effect of the potent 2,4-dinitrofluorobenzene (DNFB) hapten sensitizer with SiO2 and mTiO2 NPs on BMDC cytotoxicity, cytokine secretion and phenotype using the B7 family ligands. Results show that DNFB and mTiO2 behave similarly and exhibit proinflammatory characteristics while SiO2 promotes a naive phenotype. We observe that the B7-H3 (CD276) ligand is only expressed on CD80 + (B7-1) BMDCs. Results from adoptive transfer CHS studies, combined with BMDC phenotype analysis, point to the importance of PD-L2 expression in modulating the adaptive immune response. This work identifies metrics that can be used to predict the effects of NPs on contact allergy and to guide efforts to engineer cell-based therapies to induce hapten specific immune tolerance.
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