Mechanisms of Engineered Nanomaterial Modulation of Skin Immune Responses

项目摘要 该项目建立在我们的新发现之上，即局部应用的工程纳米材料(ENM)可以 调节皮肤的过敏性免疫反应。使用接触性超敏反应(CHS)小鼠模型 发现一些ENM抑制皮肤炎症，这与治疗相关，而其他 加剧过敏症状，表明皮肤ENM暴露的风险增加 尤其是对患有过敏性接触性皮炎(ACD)的个人。事实上，15%-20%的 美国人被诊断为ACD，占报告职业性皮肤病的95% 这是患者去看皮肤科医生的第三大常见原因。随着不断扩大的工业和 消费者对ENM的使用ACD患者同时出现的风险越来越大 通过使用纳米材料，使皮肤接触环境过敏原或化学致敏剂以及新型致敏剂 使能的产品或职业暴露。这个项目的主要目标是了解 内毒素调节皮肤过敏性免疫反应的细胞和分子机制 目前人们对此知之甚少。我们已经定义了一个早期的行动时间窗口，在这个时间窗口内 ENM发挥其作用，我们的数据表明与肥大细胞(MC)有重要联系。这个 该项目的中心假设是ENM在皮肤中发挥免疫调节作用 通过改变早期MC激活而引起的过敏反应。我们将研究ENM如何改变 利用创新的LIVE技术研究MC的激活机制及其与其他类型表皮细胞的相互作用 小鼠活体成像和新方法的常用技术。一组体外检测是 建议进一步研究新兴市场是否对跨国公司产生直接影响或通过改变间接作用 由其他类型的表皮细胞产生的旁分泌信号，从而抑制或加剧 CHS诱导反应。该项目将产生评估风险/收益所需的知识 意外/有意暴露ENM皮肤并产生预防过敏皮肤的新方法 发炎。

Project Summary This project builds on our novel finding that topically applied engineered nanomaterials (ENMs) can modulate allergic immune responses in skin. Using a contact hypersensitivity (CHS) mouse model we discovered that some ENMs suppress skin inflammation which is therapeutically relevant and others exacerbate allergic symptoms suggesting an increased hazard for cutaneous ENM exposure particularly for individuals whom suffer with allergic contact dermatitis (ACD). In fact, 15-20% of the US population is diagnosed with ACD which accounts for 95% of reported occupational skin disease and is the third most common reason patients visit a dermatologist. With the expanding industrial and consumer use of ENMs there is a growing risk that individuals with ACD may simultaneously come into skin contact with environmental allergens or chemical sensitizers and ENMs through use of nano- enabled products or from occupational exposures. The primary goal of this project is to understand the cellular and molecular mechanisms of how ENMs modulate allergic skin immune responses for which little is currently understood. We have defined an early time window of action within which ENMs exert their effects and our data suggests an important connection with mast cells (MCs). The central hypothesis of this project is that ENMs exert immunomodulatory effects in skin allergic responses by altering early MC activation. We will examine how ENMs alter the mechanisms of MC activation and their cross talk with other epidermal cell types using innovative live mouse intravital imaging and common techniques in novel ways. A panel of in vitro assays are proposed to further examine if ENMs exert a direct effect on MCs or act indirectly by altering paracrine signals generated by other epidermal cell types thereby suppressing or exacerbating the CHS elicitation response. This project will generate knowledge needed to assess the risk/benefit of unintended/intended ENM skin exposure and generate novel approaches for preventing allergic skin inflammation.