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

Authors
 Sunil K. Chauhan  ;  Yiping Jin  ;  Sunali Goyal  ;  Hyun Soo Lee  ;  Thomas A. Fuchsluger  ;  Hyung Keun Lee  ;  Reza Dana 
Citation
 BLOOD, Vol.118(17) : 4630-4634, 2011 
Journal Title
BLOOD
ISSN
 0006-4971 
Issue Date
2011
MeSH
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* ; Th17 Cells/secretion
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.
Files in This Item:
T201104944.pdf Download
DOI
10.1182/blood-2011-01-332049
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/94853
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