title: IL-23-independent induction of IL-17 from γδT cells and innate lymphoid cells promotes experimental intraocular neovascularization.
abstract: Choroidal neovascularization (CNV) is a characteristic of age-related macular degeneration. Genome-wide association studies have provided evidence that the immune system is involved in the pathogenesis of age-related macular degeneration; however, the role of inflammatory cytokines in CNV has not been established. In this study, we demonstrated that IL-17 had a strong potential for promoting neovascularization in a vascular endothelial growth factor-independent manner in laser-induced experimental CNV in mice. Infiltrated γδT cells and Thy-1(+) innate lymphoid cells, but not Th17 cells, were the main sources of IL-17 in injured eyes. IL-23 was dispensable for IL-17 induction in the eye. Instead, we found that IL-1β and high-mobility group box 1 strongly promoted IL-17 expression by γδT cells. Suppression of IL-1β and high-mobility group box 1, as well as depletion of γδT cells, reduced IL-17 levels and ameliorated experimental CNV. Our findings suggest the existence of a novel inflammatory cytokine network that promotes neovascularization in the eye.
authors: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors: Eiichi
authors: E
authors: Hasegawa
authors: Koh-Hei
authors: KH
authors: Sonoda
authors: Takashi
authors: T
authors: Shichita
authors: Rimpei
authors: R
authors: Morita
authors: Takashi
authors: T
authors: Sekiya
authors: Akihiro
authors: A
authors: Kimura
authors: Yuji
authors: Y
authors: Oshima
authors: Atsunobu
authors: A
authors: Takeda
authors: Takeru
authors: T
authors: Yoshimura
authors: Shigeo
authors: S
authors: Yoshida
authors: Tatsuro
authors: T
authors: Ishibashi
authors: Akihiko
authors: A
authors: Yoshimura
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000235:genetics; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D053760:Interleukin-23 Subunit p19 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007834:Lasers / Q000009:adverse effects; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse