TY - JOUR
T1 - A novel pro-lymphangiogenic function for Th17/IL-17
AU - Chauhan, Sunil K.
AU - Jin, Yiping
AU - Goyal, Sunali
AU - Lee, Hyun Soo
AU - Fuchsluger, Thomas A.
AU - Lee, Hyung Keun
AU - Dana, Reza
PY - 2011/10/27
Y1 - 2011/10/27
N2 - 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 andamplification of immunity in part through its induction of lymphangiogenesis.
AB - 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 andamplification of immunity in part through its induction of lymphangiogenesis.
UR - http://www.scopus.com/inward/record.url?scp=80055064696&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80055064696&partnerID=8YFLogxK
U2 - 10.1182/blood-2011-01-332049
DO - 10.1182/blood-2011-01-332049
M3 - Article
C2 - 21908425
AN - SCOPUS:80055064696
VL - 118
SP - 4630
EP - 4634
JO - Blood
JF - Blood
SN - 0006-4971
IS - 17
ER -