Exploring hair follicle-associated functions in normal and ichthyotic skin

项目总结/摘要 我们的皮肤是一个多层次的结构，作为一个保护屏障对环境。屏障功能 通常与皮肤表面相关;然而，目前尚不清楚毛囊是否也 形成一个屏障。在这里，我们已经产生了能够在空间上和时间上限制性地缺失 脂质转运蛋白ABCA 12，在患有丑角鱼鳞病（HI）的患者中发生突变， 屏障病我们将利用这些小鼠作为工具来研究毛囊对皮肤的贡献 稳态，同时检查如何毛囊相关的过程中扰乱HI。我们假设 毛囊可以通过以下4种方式影响正常皮肤和鱼鳞病皮肤：1）上部毛囊可以 直接提供屏障功能。2)毛囊可能影响邻近表皮的行为， 细胞自主。3)上部毛囊可能是快速脱屑的部位， 皮脂4)上部毛囊可呈现伤口样状态，并在表皮生长时向表皮贡献细胞。 屏障破坏总之，这些研究将有助于我们了解基础知识， 上毛囊区域，一个研究较少的皮肤区域，在疾病如痤疮中受到干扰， 化脓性汗腺炎和毛发角化病。同时，这部作品也将HI从一部小说中考虑 从一个角度，重点放在毛囊上。最后，我们的研究将描述一个可行的，免疫活性小鼠 HI模型，以探索新的治疗方法。

Project Summary / Abstract Our skin is a multi-layered structure that acts as a protective barrier against the environment. Barrier function is typically associated with the surface of the skin; however, it is currently unclear whether the hair follicle also forms a barrier. Here, we have generated mice that enable spatially and temporally restricted deletion of the lipid transporter ABCA12, which is mutated in patients with harlequin ichthyosis (HI), the most severe skin barrier disease. We will utilize these mice as tools to study the contributions of the hair follicle to skin homeostasis, while examining how hair follicle-related processes are perturbed in HI. We hypothesize that the hair follicle may affect both normal and ichthyotic skin in the following 4 ways: 1) The upper hair follicle may directly provide barrier function. 2) The hair follicle may influence the behavior of the adjacent epidermis non- cell autonomously. 3) The upper hair follicle is likely a site of rapid desquamation that allows for the release of sebum. 4) The upper hair follicle may assume a wound-like state and contribute cells to the epidermis upon barrier disruption. Altogether, these studies will contribute fundamental knowledge to our understanding of the upper hair follicle domain, a poorly studied region of the skin that is perturbed in diseases such as acne, hidradenitis suppurativa and keratosis pilaris. At the same time, this work will also consider HI from a novel angle, with a focus on the hair follicle. Finally, our studies will characterize a viable, immunocompetent mouse model of HI to explore novel therapies.