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

Immunity. 2019 Mar 19;50(3):655-667.e4. 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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Chemokine CXCL5 / metabolism*
  • Epidermal Cells / metabolism
  • Epidermis / metabolism*
  • Epithelial Cells / metabolism
  • Hair / metabolism
  • Hair Follicle / metabolism*
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Regeneration / physiology*
  • Stem Cells / metabolism
  • T-Lymphocytes, Regulatory / metabolism*


  • Chemokine CXCL5
  • Cxcl5 protein, mouse
  • Il17a protein, mouse
  • Interleukin-17