Abstract：
Disorders in the regulatory arm of the adaptive immune system result in autoimmune-mediated diseases. While systemic immunosuppression is the prevailing approach to manage them, it fails to achieve long-lasting remission due to concomitant suppression of the regulatory arm and carries the risk of heightened susceptibility to infections and malignancies. Alopecia areata is a condition characterized by localized hair loss due to autoimmunity. The accessibility of the skin allows local rather than systemic intervention to avoid broad immunosuppression. It is hypothesized that the expansion of endogenous regulatory T cells (Tregs) at the site of antigen encounter can restore the immune balance and generate a long-lasting tolerogenic response. A hydrogel microneedle (MN) patch is therefore utilized for delivery of CCL22, a Treg-chemoattractant, and IL-2, a Treg survival factor to amplify them. In an immune-mediated murine model of alopecia, local bolstering of Treg numbers is shown, leading to sustained hair regrowth and attenuation of inflammatory pathways. In a humanized skin transplant mouse model, expansion of Tregs within human skin is confirmed without engendering peripheral immunosuppression. The patch offers high-loading capacity and shelf-life stability for prospective clinical translation. By harmonizing immune responses locally, the aim is to reshape the landscape of autoimmune skin disease management.
摘要：
适应性免疫系统的调节臂中的紊乱导致自身免疫介导的疾病。虽然全身免疫抑制是管理它们的主要方法，它不能实现持久的缓解，由于伴随抑制的调节臂，并具有增加的易感性感染和恶性肿瘤的风险。斑秃是一种特征在于由于自身免疫引起的局部脱发的病症。皮肤的可接近性提供了局部而非全身干预以避免广泛的免疫抑制的机会。我们假设内源性调节性T细胞（Tregs）在抗原相遇部位的扩增可以恢复免疫平衡并产生持久的致耐受性反应。因此，我们使用水凝胶微针（MN）贴片来递送CCL22，一种用于Tregs的化学引诱物，和IL-2，一种Treg存活因子来扩增它们。在免疫介导的脱发鼠模型中，我们显示Treg数量的局部支持导致持续的毛发再生和炎症途径的减弱。在人源化皮肤移植小鼠模型中，我们证实了Tregs在人皮肤内的扩张，而不会导致外周免疫抑制。MN贴片为前瞻性临床翻译提供了高负载能力和保质期稳定性。通过局部协调免疫反应，我们渴望重塑自身免疫性皮肤病管理的景观。本文受版权保护。保留所有权利。
