Engineering the Skin Immune System to Induce Systemic Immune Responses

项目总结/摘要： 皮肤作为一种有效的免疫器官发挥作用， 微环境是一个有吸引力的目标，可以在局部工程诱导和调节 全身免疫反应。年龄的增长与免疫功能的变化有关 （免疫衰老），导致对疾病的易感性增加和疫苗质量差 老年人的反应。这项建议旨在汇集最近和重要的 皮肤病学和皮肤生物学的进步，以解决人类健康的关键问题。这里我们 特别关注皮肤微环境和皮肤免疫调节策略。 总体方法是利用临床适用的可溶解微针阵列递送 我们开发了一个平台，用于本地设计高度适应性和免疫反应的皮肤， 微环境具体来说，我们建议调节局部免疫调节回路中的 皮肤，以能够诱导和调节全身免疫应答。我们的研究 建议将研究局部递送的免疫调节剂对机制的影响 在年轻和老年皮肤中潜在的皮肤免疫调节。重要的是，我们的研究包括 使用活体人类皮肤的转化研究，使新的皮肤 免疫调节策略进入临床试验。拟议的研究将导致更好的 了解皮肤免疫生物学，特别是与开发安全和 可预测的皮肤免疫工程策略，以调节全身免疫反应， 寿命

PROJECT SUMMARY / ABSTRACT: The skin functions as a potent immune organ, rendering the readily accessible cutaneous microenvironment an attractive target that can be locally engineered to induce and regulate systemic immune responses. Increasing age is associated with changes in immune function (immunosenescence) that result in increased susceptibility to diseases and poor vaccine responses in older adults. This proposal is designed to bring together very recent and significant advances in dermatology and skin biology to address critical problems in human health. Here, we specifically focus on the skin microenvironment and strategies for cutaneous immunomodulation. The overall approach is to utilize a clinically applicable dissolvable microneedle array delivery platform we have developed to locally engineer the highly adaptive and immunoresponsive skin microenvironment. Specifically, we propose to modulate local immune regulatory circuits in the skin to enable the induction and regulation of systemic immune responses. The studies we propose will investigate the effect of locally delivered immune modulators on the mechanisms underlying cutaneous immune regulation in young and aged skin. Importantly, our studies include translational studies using living human skin to enable the rapid advancement of novel cutaneous immunomodulation strategies into clinical trials. The proposed studies will result in a better understanding of skin immunobiology specifically relevant to the development of safe and predictable skin immunoengineering strategies to regulate systemic immune responses across the lifespan.