|LIU, QIONG - Children'S Nutrition Research Center (CNRC)|
|SMITH, C. WAYNE - Children'S Nutrition Research Center (CNRC)|
|WANYU, ZHANG - Baylor College Of Medicine|
|BURNS, ALAN - Baylor College Of Medicine|
|LI, ZHIJIE - Baylor College Of Medicine|
Submitted to: American Journal of Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/5/2012
Publication Date: 8/1/2012
Citation: Liu, Q., Smith, C., Wanyu, Z., Burns, A.R., Li, Z. 2012. NK cells modulate the inflammatory response to corneal epithelial abrasion and thereby support wound healing. American Journal of Pathology. 181(2):452-462.
Interpretive Summary: Diabetes, a condition where the body cannot use blood sugar efficiently, often results in among other things poor wound healing. The mechanisms of normal wound healing were studied using an animal model to analyze how a specific set of white blood cells called NK cells control the level of inflammation induced by injury to body tissues. We found that these cells produce a protein on their surface that acts to resolve tissue inflammation. Findings from this study are transferrable to increasing our knowledge base for human nutrition by providing a precise and clinically important research model currently used to investigate the mechanisms of normal wound healing disrupted by diabetes.
Technical Abstract: Natural killer cells are lymphocytes of the innate immune system that have crucial cytotoxic and regulatory roles in adaptive immunity and inflammation. Herein, we consider a role for these cells in corneal wound healing. After a 2-mm central epithelial abrasion of the mouse cornea, a subset of classic natural killer cells migrated into the limbus and corneal stroma, peaking at 24 hours with an eightfold increase over baseline. Depletion of gamma delta T cells significantly reduced natural killer cell accumulation (>70%; P < 0.01); however, in neutrophil-depleted animals, natural killer cell influx was normal. Isolated spleen natural killer cells migrated to the wounded cornea, and this migration was reduced by greater than 60% (P < 0.01) by ex vivo antibody blocking of natural killer cell CXCR3 or CCR2. Antibody-induced depletion of natural killer cells significantly altered the inflammatory reaction to corneal wounding, as evidenced by a 114% increase (P < 0.01) in neutrophil influx at a time when acute inflammation is normally waning. Functional blocking of NKG2D, an activating receptor for natural killer cell cytotoxicity and cytokine secretion, did not inhibit natural killer cell immigration, but significantly increased neutrophil influx. Consistent with excessive neutrophil accumulation, natural killer depletion and blocking of NKG2D also inhibited corneal nerve regeneration and epithelial healing (P < 0.01). Findings of this study suggest that natural killer cells are actively involved in corneal healing by limiting the innate acute inflammatory reaction to corneal wounding.