NK Cells Modulate the Inflammatory Response to Corneal Epithelial Abrasion and Thereby Support Wound Healing
Year: 2012
Type: article
Abstract: Natural killer (NK) 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 NK cells migrated into the limbus and corneal stroma, peaking at 24 hours with an eightfold increase over baseline. Depletion of γδ T cells significantly reduced NK cell accumulation (>70%; P < 0.01); however, in neutrophil-depleted animals, NK cell influx was normal. Isolated spleen NK cells migrated to the wounded cornea, and this migration was reduced by greater than 60% (P < 0.01) by ex vivo antibody blocking of NK cell CXCR3 or CCR2. Antibody-induced depletion of NK 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 NK cell cytotoxicity and cytokine secretion, did not inhibit NK cell immigration, but significantly increased neutrophil influx. Consistent with excessive neutrophil accumulation, NK depletion and blocking of NKG2D also inhibited corneal nerve regeneration and epithelial healing (P < 0.01). Findings of this study suggest that NK cells are actively involved in corneal healing by limiting the innate acute inflammatory reaction to corneal wounding.
Source: American Journal Of Pathology
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,800
Awards: G1028288209, 妊娠相关激素对眼免疫赦免调控的细胞和分子机制, CORE-VISION RESEARCH, G2201816791, G2312665263, Leukocyte Migration in Wounded Cornea, G302913688, G4227483027, G5006730111, G5178220043, G59541392, G6056933206, G6064340350, Ocular Surface Injury: Inflammatory Cascade and Healing of Corneal Wounds, G6791272909, G7401028427, 血小板介导角膜上皮创伤修复的细胞和分子机制, G7988606049, G8585343246, G9000032451, G9000302836
OpenAlex ID: W2012159552
