1. Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair-Follicle-Stem-Cell Differentiation During Skin-Barrier Repair.
- Author
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Mathur AN, Zirak B, Boothby IC, Tan M, Cohen JN, Mauro TM, Mehta P, Lowe MM, Abbas AK, Ali N, and Rosenblum MD
- Subjects
- Animals, Epidermal Cells metabolism, Epithelial Cells metabolism, Hair metabolism, Mice, Mice, Inbred C57BL, Stem Cells metabolism, Cell Differentiation physiology, Chemokine CXCL5 metabolism, Epidermis metabolism, Hair Follicle metabolism, Interleukin-17 metabolism, Regeneration physiology, T-Lymphocytes, Regulatory metabolism
- Abstract
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 SC 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 SC 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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