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

Eiichi Hasegawa, Koh Hei Sonoda, Takashi Shichita, Rimpei Morita, Takashi Sekiya, Akihiro Kimura, Yuji Oshima, Atsunobu Takeda, Takeru Yoshimura, Shigeo Yoshida, Tatsuro Ishibashi, Akihiko Yoshimura

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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.

Original languageEnglish
Pages (from-to)1778-1787
Number of pages10
JournalJournal of Immunology
Volume190
Issue number4
DOIs
Publication statusPublished - 2013 Feb 15

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Interleukin-23
Interleukin-17
Choroidal Neovascularization
Lymphocytes
T-Lymphocytes
Macular Degeneration
Interleukin-1
Cytokines
Th17 Cells
Genome-Wide Association Study
Vascular Endothelial Growth Factor A
Immune System
Lasers

ASJC Scopus subject areas

  • Immunology

Cite this

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

In: Journal of Immunology, Vol. 190, No. 4, 15.02.2013, p. 1778-1787.

Research output: Contribution to journalArticle

Hasegawa, E, Sonoda, KH, Shichita, T, Morita, R, Sekiya, T, Kimura, A, Oshima, Y, Takeda, A, Yoshimura, T, Yoshida, S, Ishibashi, T & Yoshimura, A 2013, 'IL-23-independent induction of IL-17 from γδT cells and innate lymphoid cells promotes experimental intraocular neovascularization', Journal of Immunology, vol. 190, no. 4, pp. 1778-1787. https://doi.org/10.4049/jimmunol.1202495
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. / IL-23-independent induction of IL-17 from γδT cells and innate lymphoid cells promotes experimental intraocular neovascularization. In: Journal of Immunology. 2013 ; Vol. 190, No. 4. pp. 1778-1787.
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