Engineering the Skin Immune System to Induce Systemic Immune Responses

项目摘要/摘要： 皮肤的功能是一个强大的免疫器官，使容易接触到的皮肤 微环境：一个有吸引力的目标，可以在当地进行工程来诱导和调节 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)导致疾病易感性增加和疫苗质量不佳 老年人的反应。这项建议旨在将非常新的和有意义的 皮肤病学和皮肤生物学的进展，以解决人类健康中的关键问题。在这里，我们 特别关注皮肤微环境和皮肤免疫调节策略。 总的方法是利用临床上适用的可溶解微针阵列输送 我们开发的平台用于局部设计高度适应性和免疫反应性的皮肤 微环境。具体地说，我们建议调节局部免疫调节电路在 皮肤能够诱导和调节全身免疫反应。我们的研究 Proposal将调查局部传递的免疫调节剂对机制的影响 年轻皮肤和老年皮肤潜在的皮肤免疫调节。重要的是，我们的研究包括 利用活体人类皮肤进行的转译研究使新型皮肤能够快速发展 将免疫调节策略纳入临床试验。拟议的研究将产生更好的 对皮肤免疫生物学的了解，特别是与发展安全和 可预测的皮肤免疫工程策略，以调节全身免疫反应 生命的长短。

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.