title: A novel pro-lymphangiogenic function for Th17/IL-17.
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.
authors: Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. sunil.chauhan@schepens.harvard.edu
authors: Sunil K
authors: SK
authors: Chauhan
authors: Yiping
authors: Y
authors: Jin
authors: Sunali
authors: S
authors: Goyal
authors: Hyun Soo
authors: HS
authors: Lee
authors: Thomas A
authors: TA
authors: Fuchsluger
authors: Hyung Keun
authors: HK
authors: Lee
authors: Reza
authors: R
authors: Dana
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015352:Dry Eye Syndromes / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D042583:Lymphangiogenesis / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D058504:Th17 Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D020381:Interleukin-17