NK Cells Are Necessary For Recovery Of Corneal CD11c~+ Dendritic Cells After Epithelial Abrasion Injury

Mechanisms controlling CD11c~+ MHC?~+ dendritic cells(DC)during corneal epithelial wound healing were investigated in a murine model of corneal abrasion.In this murine model,CD11c~+ MHC?~+ cells progressively increased,peaking at 48 hours after epithelial abrasion.Injury to the corneal surface could also induce influx of NKp46+ CD3-natural killer(NK)cells.We analyzed their possible influence on the CD11c~+ MHC?~+ dendritic cells recently shown to support epithelial tissue repair.Selective depletion of NKp46+ CD3-natural killer(NK)cells that normally migrate into the cornea after epithelial abrasion resulted in>85%reduction of the epithelial CD11c~+ MHC?~+ dendritic cells(DC)normally present during and after epithelial wound closure.Intravenous transfer of spleen NK cells into NK cell-depleted mice significantly restored levels of corneal epithelial DC(p<0.01).Immigrated NK cells were predominately positive for interferony(IFN?),and topical corneal anti-IFNy reduced epithelial DC by 79%(p<0.01).IFNy-deficient mice(Ifn-/-)had 69%fewer DC than wildtype controls(p<0.01),and topical recombinant IFNy applied to NK cell-depleted corneas significantly increased epithelial DC(p<0.01).The contribution of intercellular adhesion molecule-1(ICAM-1),an adhesion molecule involved in leukocyte migration expressed on healing corneal epithelium,was evaluated.ICAM-1-deficient mice(Icam-I-/-)exhibited>70%reduction in epithelial DC recovery in the first 48 hours after epithelial abrasion(p<0.01).These interventions reveal an early turnover of dendritic cells in the epithelium after injury,and NK cells,ICAM-1,IFN? and CX3CL1 are necessary for the immigration phase of this turnover.