CCL20, γδ T cells, and IL-22 in corneal epithelial healing

FASEB J. 2011 Aug;25(8):2659-68. doi: 10.1096/fj.11-184804. Epub 2011 Apr 25.

Abstract

After corneal epithelial abrasion, leukocytes and platelets rapidly enter the corneal stroma, and CCR6(+) IL-17(+) γδ T cells migrate into the epithelium. γδ T-cell-deficient (TCRδ(-/-)) mice have significantly reduced inflammation and epithelial wound healing. Epithelial CCL20 mRNA increased 19-fold at 3 h, and protein increased ∼ 16-fold at 6 h after injury. Systemic or topical treatment of wild-type C57BL/6 mice with anti-CCL20 reduced γδ T-cell accumulation in the cornea by >50% with a concomitant decrease in epithelial healing and stromal inflammation. In addition to CCR6 and IL-17, corneal γδ T cells stained positively for RORγt, IL-23R, and IL-22. Anti-IL-22 reduced peak cell division of the healing epithelium by 52%. Treatment of TCRδ(-/-) mice with rIL-22 significantly promoted wound closure, with peak epithelial cell division increased >3-fold. In addition, rIL-22 restored neutrophil and platelet influx in the TCRδ(-/-) mice to wild-type levels and increased CXCL1 production by wounded corneal explants >2-fold. These results indicate that an important aspect of the healing response to corneal epithelial abrasion includes CCL20-dependent influx of CCR6(+) IL-17(+) IL-22(+) γδ T cells and that IL-22 contributes to the inflammatory response and promotes epithelial healing.

Publication types

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

MeSH terms

  • Animals
  • Chemokine CCL20 / genetics*
  • Chemokine CCL20 / metabolism*
  • Chemokine CXCL1 / metabolism
  • Epithelium, Corneal / drug effects
  • Epithelium, Corneal / immunology*
  • Epithelium, Corneal / injuries
  • Epithelium, Corneal / pathology
  • Female
  • Genes, T-Cell Receptor delta
  • Interleukin-17 / metabolism
  • Interleukins / antagonists & inhibitors
  • Interleukins / metabolism*
  • Interleukins / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / deficiency
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Receptors, CCR6 / metabolism
  • Recombinant Proteins / pharmacology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology
  • Wound Healing / drug effects
  • Wound Healing / genetics
  • Wound Healing / immunology

Substances

  • CCL20 protein, mouse
  • CCR6 protein, mouse
  • Chemokine CCL20
  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • Interleukin-17
  • Interleukins
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, CCR6
  • Recombinant Proteins
  • interleukin-22