Interferon-γ Up-Regulates Major-Histocompatibility-Complex Class I-Related Chain A Expression and Enhances Major-Histocompatibility-Complex Class I-Related Chain A-Mediated Cytolysis of Human Corneal Epithelium by Natural Killer CellsIn Vitro

Abstract

Natural killer (NK) cells are important in the ocular surface innate response against viral and bacterial infection. Major-histocompatibility-complex class I-related chain A (MICA) antigens are ligands of natural killer group 2D, an activating or coactivating receptor expressed on NK cells. Recent studies demonstrated that interferon-gamma (IFN-γ) could modulate MICA expression in tumor cells. However, little is known about MICA expression and regulation in human corneal epithelium. Our study assessed whether the proinflammatory cytokine, IFN-γ, affects MICA expression in human corneal epithelium. We identified low levels of surface MICA expression in corneal epithelium using flow cytometry. IFN-γ promoted surface MICA expression in corneal epithelium and increased soluble MICA levels in a dose-dependent manner. IFN-γ also enhanced NK cell-mediated cytotoxicity against the corneal epithelium. Anti-MICA antibodies could further block this process. In summary, we describe a novel IFN-γ function in the regulation of the innate response in ocular surfaces.