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Immunity. 2019 Mar 19;50(3):655-667.e4. doi: 10.1016/j.immuni.2019.02.013.

Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair-Follicle-Stem-Cell Differentiation During Skin-Barrier Repair.

Author information

1
Department of Dermatology, University of California, San Francisco, CA, USA.
2
Department of Pathology, University of California, San Francisco, CA, USA.
3
Department of Dermatology, University of California, San Francisco, CA, USA. Electronic address: michael.rosenblum@ucsf.edu.

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.

KEYWORDS:

CXCL5; IL-17; Lrg5; barrier repair; epidermis; hair follicle stem cells; regulatory T cell (Treg); skin; stem cell

PMID:
30893588
PMCID:
PMC6507428
[Available on 2020-03-19]
DOI:
10.1016/j.immuni.2019.02.013
[Indexed for MEDLINE]

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