title: NK cells are necessary for recovery of corneal CD11c+ dendritic cells after epithelial abrasion injury.
abstract: Mechanisms controlling CD11c(+) MHCII(+) DCs during corneal epithelial wound healing were investigated in a murine model of corneal abrasion. Selective depletion of NKp46(+) CD3- NK cells that normally migrate into the cornea after epithelial abrasion resulted in >85% reduction of the epithelial CD11c(+) MHCII(+) DCs, normally present during and after epithelial wound closure. Transfer (i.v.) of spleen NK cells into NK cell-depleted mice significantly restored levels of corneal epithelial DCs (P<0.01). Immigrated NK cells were predominately positive for IFN-γ, and topical corneal anti-IFN-γ reduced epithelial DCs by 79% (P<0.01). IFN-γ(-/-) mice had 69% fewer DCs than WT controls (P<0.01), and topical rIFN-γ applied to NK cell-depleted corneas increased epithelial DCs significantly (P<0.01). The contribution of ICAM-1, an adhesion molecule involved in leukocyte migration, expressed on healing corneal epithelium, was evaluated. ICAM-1(-/-) mice exhibited >70% reduction in epithelial DC recovery in the first 48 h after epithelial abrasion (P<0.01). These interventions reveal an early turnover of DCs in the epithelium after injury, and ICAM-1, NK cells, and IFN-γ are necessary for the immigration phase of this turnover.
authors.affiliation: Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Hospital, Tianjin, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Li
authors.forename: Nida
authors.initials: N
authors.lastname: Hassan
authors.forename: Pooja
authors.initials: P
authors.lastname: Mehta
authors.forename: Alan R
authors.initials: AR
authors.lastname: Burns
authors.forename: Xin
authors.initials: X
authors.lastname: Tang
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Smith
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D039521:CD11c Antigen / Q000032:analysis*; D002465:Cell Movement; D003713:Dendritic Cells / Q000473:pathology*; D019573:Epithelium, Corneal / Q000293:injuries* / Q000502:physiology; D005260:Female; D019676:Genes, T-Cell Receptor delta; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology; D007518:Isoantibodies / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000502:physiology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D039521:CD11c Antigen; D007518:Isoantibodies; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma
keywords: ICAM-1; IFN-γ; cornea; healing