γδ T cells and corneal wound healing - CANCELLED

Efficient wound healing of the cornea involves restoration of surface epithelium, regeneration of the subepithelial sensory nerve plexus and recovery of stromal keratocytes.  Epithelial and sensory nerve injury in a murine model induces an acute inflammatory response in the limbal vessels involving migration of T cells, neutrophils, monocytes and platelets into the connective tissue stroma. The most abundant lymphocytes accumulating in the corneal epithelium are IL-17+ IL-22+ CCR6+ γδ T cells dependent on epithelial production of CCL20. These cells appear necessary for the inflammatory response since TCRδ-/- mice and wildtype mice following antibody-dependent depletion of γδ T cells have profoundly reduced corneal inflammation as well as significantly delayed epithelial wound closure, sensory nerve regeneration and keratocyte recovery. Experimental evidence indicates that IL-17A significantly contributes to corneal accumulation of neutrophils and platelets, cells containing VEGF-A, a trophic factor for early neurite regeneration. Anti-VEGF-A markedly inhibits corneal sensory nerve regeneration. Additional studies indicate that IL-22 promotes corneal epithelial proliferation and migration. Thus, in a murine model of corneal injury, an inflammatory cascade beneficial to wound healing is apparently promoted by epithelial production of CCL20 attracting IL-17+ IL-22+ CCR6+ γδ T cells into the cornea.

Speaker: C. Wayne Smith, MD, Professor, Department of Pediatrics, Immunology Head, Section of Leukocyte Biology, Baylor College of Medicine, Children's Nutrition Research Center, Houston, Texas
Host: Karsten Gronert

Room 489