IL-17 and VEGF are necessary for efficient corneal nerve regeneration

Am J Pathol. 2011 Mar;178(3):1106-16. doi: 10.1016/j.ajpath.2010.12.001.


The contribution of acute inflammation to sensory nerve regeneration was investigated in the murine cornea using a model of corneal abrasion that removes the stratified epithelium and subbasal nerve plexus. Abrasion induced accumulation of IL-17(+) CCR6(+) γδ T cells, neutrophils, and platelets in the cornea followed by full restoration of the epithelium and ∼19% regeneration of sensory nerves within 96 hours. Mice deficient in γδ T cells (TCRδ(-/-)) or wild-type mice treated systemically with anti-IL-17 had >50% reduction in leukocyte and platelet infiltration and >50% reduction in nerve regeneration. Strategies used to prevent neutrophil and platelet accumulation (eg, wild-type mice treated with anti-Ly6G or anti-GP1bα antibody to deplete neutrophils or platelets) also resulted in >50% reductions in corneal nerve density. Infiltrating neutrophils and platelets stained positively for VEGF-A, tissue levels of VEGF-A peaked coincidentally with peak tissue levels of neutrophils and platelets, depletion of neutrophils before injury reduced tissue VEGF-A levels by >70%, and wild-type mice treated systemically with anti-VEGF-A antibody exhibited >80% reduction in corneal nerve regeneration. Given the known trophic effects of VEGF-A for neurite growth, the results in this report demonstrate a previously unrecognized beneficial role for the γδ T cell-dependent inflammatory cascade involving IL-17, neutrophils, platelets, and VEGF-A in corneal nerve regeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blood Platelets / metabolism
  • Cornea / innervation*
  • Cornea / metabolism*
  • Cornea / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-17 / metabolism*
  • Mice
  • Nerve Regeneration*
  • Neutrophils / metabolism
  • P-Selectin / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / deficiency
  • Vascular Endothelial Growth Factor A / metabolism*


  • Interleukin-17
  • P-Selectin
  • Receptors, Antigen, T-Cell, gamma-delta
  • Vascular Endothelial Growth Factor A
  • Intercellular Adhesion Molecule-1