Department of Dermatology, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Rachel E. Benedeck
Department of Dermatology, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Matthew T. Mattoon
Department of Dermatology, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
Jamie K. Peterson
Department of Dermatology, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
Arlee L. Mesler
Department of Dermatology, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
Natalia A. Veniaminova
Department of Dermatology, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
Danielle J. Gardon
Department of Dermatology, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
Shih-Ying Tsai
Department of Dermatology, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
Yoshikazu Uchida
Department of Food Science and Nutrition, and Convergence Program of Material Science for Medicine and Pharmaceutics, Hallym University, Chuncheon, Republic of Korea
Sunny Y. Wong
Department of Dermatology, Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA; Corresponding author
Summary: Our skin provides a protective barrier that shields us from our environment. Barrier function is typically associated with the interfollicular epidermis; however, whether hair follicles influence this process remains unclear. Here, we utilize a potent genetic tool to probe barrier function by conditionally ablating a quintessential epidermal barrier gene, Abca12, which is mutated in the most severe skin barrier disease, harlequin ichthyosis. With this tool, we deduced 4 ways by which hair follicles modulate skin barrier function. First, the upper hair follicle (uHF) forms a functioning barrier. Second, barrier disruption in the uHF elicits non-cell-autonomous responses in the epidermis. Third, deleting Abca12 in the uHF impairs desquamation and blocks sebum release. Finally, barrier perturbation causes uHF cells to move into the epidermis. Neutralizing IL-17a, whose expression is enriched in the uHF, partially alleviated some disease phenotypes. Altogether, our findings implicate hair follicles as multi-faceted regulators of skin barrier function.
