|Gao, Yuan -|
|Li, Zhijie -|
|Hassan, Nida -|
|Mehta, Pooja -|
|Burns, Alar -|
|Tang, Xin -|
|Smith, Clifton -|
Submitted to: Journal of Leukocyte Biology
Publication Type: Review Article
Publication Acceptance Date: May 2, 2013
Publication Date: August 1, 2013
Citation: Gao, Y., Li, Z., Hassan, N., Mehta, P., Burns, A.R., Tang, X., Smith, C.W. 2013. NK cells are necessary for recovery of corneal CD11c+ dendritic cells after epithelial abrasion injury. Journal of Leukocyte Biology. 94:(2)343-351. Interpretive Summary: Wound healing is a complex process that involves different types of white blood cells. The problem addressed in this study was to determine specific mechanisms by which the white blood cells are necessary for healing. We found that at least three types of white blood cells are important, and that they act in sequence. The first are called gamma delta T cells, and they are necessary for the second type, called NK cells, which are in turn necessary for the third type, called dendritic cells. The importance of this work is that it provides basic scientific information necessary for designing future studies on how to promote wound healing in conditions such as obesity and diabetes.
Technical 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-gamma, and topical corneal anti-IFN-gamma reduced epithelial DCs by 79% (P<0.01). IFN-gamma(-/-) mice had 69% fewer DCs than WT controls (P<0.01), and topical rIFN-gamma 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-gamma are necessary for the immigration phase of this turnover.