Exploring hair follicle-associated functions in normal and ichthyotic skin

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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.