Treg cell control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair Follicle Stem Cell Differentiation into Epithelial Cells for Skin Barrier Repair

• Published in: Immunity (Cambridge, Mass.) Vol. 50; no. 3; pp. 655 - 667.e4
• Main Authors: Mathur, Anubhav N., Zirak, Bahar, Boothby, Ian C., Tan, Madge, Cohen, Jarish N., Mauro, Thea M., Mehta, Pooja, Lowe, Margaret, Abbas, Abul K., Ali, Niwa, Rosenblum, Michael D.
• Format: Journal Article
• Language: English
• Published: 19.03.2019
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2019.02.013

Restoration of barrier tissue integrity after injury is dependent on the function of immune cells and stem cells (SCs) residing in the tissue. In response to skin injury, hair follicle stem cells (HFSCs), normally poised for hair generation, are recruited to the site of injury and differentiate into cells that repair damaged epithelium. We used a stem cell fate mapping approach to examine the contribution of regulatory T (Treg) cells to epidermal barrier repair after injury. Depletion of Treg cells impaired skin barrier regeneration and was associated with a Th17 inflammatory response and failed HFSC differentiation. In this setting, damaged epithelial cells preferentially expressed the neutrophil chemoattractant CXCL5, and blockade of CXCL5 or neutrophil depletion restored barrier function and stem cell differentiation after epidermal injury. Thus, Treg cell regulation of localized inflammation enables HFSC differentiation and thereby skin barrier regeneration, with implications for the maintenance and repair of other barrier tissues. In response to skin injury, hair follicle stem cells (HFSCs) differentiate into epithelial cells that contribute to the repair of damaged epithelium. Mathur et al. show that regulatory T cells facilitate HFSC differentiation via the control of the local inflammatory environment and specifically, the prevention of an over-exuberant Th17 and neutrophil response mediated by CXCL5.