A novel pro-lymphangiogenic function for Th17/IL-17

Blood. 2011 Oct 27;118(17):4630-4. doi: 10.1182/blood-2011-01-332049. Epub 2011 Sep 8.

Abstract

Th17 cells, in addition to their proinflammatory functions, have been recognized as potent inducers of angiogenesis in autoimmune diseases and malignancies. In the present study, we demonstrate distinct mechanisms by which IL-17 induces lymphangiogenesis. Using the mouse cornea micropocket and cell culture assays, our data demonstrate that IL-17 directly promotes growth of lymphatic vessels by inducing increased expression of prolymphangiogenic VEGF-D and proliferation of lymphatic endothelial cells. However, IL-17-induced growth of blood vessels is primarily mediated through IL-1β secretion by IL-17-responsive cells. Furthermore, in vivo blockade of IL-17 in a preclinical model of Th17-dominant autoimmune ocular disease demonstrates a significant reduction in the corneal lymphangiogenesis and in the progression of clinical disease. Taken together, our findings demonstrate a novel prolymphangiogenic function for Th17/IL-17, indicating that IL-17 can promote the progression and amplification of immunity in part through its induction of lymphangiogenesis.

Publication types

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

MeSH terms

  • Animals
  • Autoimmune Diseases / complications
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Cornea / immunology
  • Cornea / metabolism
  • Cornea / pathology
  • Culture Media, Conditioned / pharmacology
  • Dry Eye Syndromes / etiology
  • Dry Eye Syndromes / genetics
  • Dry Eye Syndromes / metabolism
  • Dry Eye Syndromes / pathology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / physiology
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Interleukin-17 / pharmacology
  • Interleukin-17 / physiology*
  • Lymphangiogenesis / genetics*
  • Lymphangiogenesis / immunology*
  • Lymphangiogenesis / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Th17 Cells / metabolism
  • Th17 Cells / pathology
  • Th17 Cells / physiology*

Substances

  • Culture Media, Conditioned
  • Interleukin-17