title: CCL20, γδ T cells, and IL-22 in corneal epithelial healing.
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.
authors.affiliation: Section of Leukocyte Biology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Li
authors.forename: Alan R
authors.initials: AR
authors.lastname: Burns
authors.forename: Sarah Byeseda
authors.initials: SB
authors.lastname: Miller
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Smith
mesh_terms: D000818:Animals; D054418:Chemokine CCL20 / Q000235:genetics* / Q000378:metabolism*; D054360:Chemokine CXCL1 / Q000378:metabolism; D019573:Epithelium, Corneal / Q000187:drug effects / Q000276:immunology* / Q000293:injuries / Q000473:pathology; D005260:Female; D019676:Genes, T-Cell Receptor delta; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D054399:Receptors, CCR6 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D054418:Chemokine CCL20; D054360:Chemokine CXCL1; D020381:Interleukin-17; D007378:Interleukins; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054399:Receptors, CCR6; D011994:Recombinant Proteins; D000097043:Interleukin-22; C493447:CCL20 protein, mouse; C498126:CCR6 protein, mouse; C475895:Cxcl1 protein, mouse