IL-23-independent induction of IL-17 from γδT cells and innate lymphoid cells promotes experimental intraocular neovascularization

• Published in: The Journal of immunology (1950) 2013-02, Vol.190 (4), p.1778-1787
• Main Authors: Hasegawa, Eiichi, Sonoda, Koh-Hei, Shichita, Takashi, Morita, Rimpei, Sekiya, Takashi, Kimura, Akihiro, Oshima, Yuji, Takeda, Atsunobu, Yoshimura, Takeru, Yoshida, Shigeo, Ishibashi, Tatsuro, Yoshimura, Akihiko
• Format: Article
• Language: English
• Subjects: Animals; Choroidal Neovascularization - genetics; Choroidal Neovascularization - immunology; Choroidal Neovascularization - pathology; Disease Models, Animal; Immunity, Innate - genetics; Interleukin-17 - antagonists & inhibitors; Interleukin-17 - biosynthesis; Interleukin-17 - physiology; Interleukin-23 Subunit p19 - deficiency; Interleukin-23 Subunit p19 - genetics; Interleukin-23 Subunit p19 - physiology; Lasers - adverse effects; Lymphocytes - immunology; Lymphocytes - metabolism; Lymphocytes - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Antigen, T-Cell, gamma-delta - biosynthesis; Receptors, Antigen, T-Cell, gamma-delta - genetics; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Vascular Endothelial Growth Factor A - genetics
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1202495

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.