July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Induced pluripotent stem cells-derived suppressor cells ameliorate experimental autoimmune uveoretinitis in mice
Author Affiliations & Notes
  • Keitaro Hase
    Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  • Kenichi Namba
    Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  • Nobuyoshi Kitaichi
    Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo, Japan
  • Daiju Iwata
    Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  • Hyuma Tsuji
    Division of Immunobiology, Institute for Genetic Medicine, Sapporo, Japan
  • Haruka Wada
    Division of Immunobiology, Institute for Genetic Medicine, Sapporo, Japan
  • Ken-ichiro Seino
    Division of Immunobiology, Institute for Genetic Medicine, Sapporo, Japan
  • Susumu Ishida
    Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  • Footnotes
    Commercial Relationships   Keitaro Hase, None; Kenichi Namba, AbbVie (F), Eisai Co., Ltd (F), Mitsubishi Tanabe Pharma Corporation (F); Nobuyoshi Kitaichi, None; Daiju Iwata, None; Hyuma Tsuji, None; Haruka Wada, None; Ken-ichiro Seino, None; Susumu Ishida, Alcon Japan Ltd. (F), Alpha Communication (F), Bayer Yakuhin, Ltd. (F), Bonac Co., Ltd. (P), Chugai Pharmaceutical Co., Ltd. (P), Kowa Pharmaceutical Co., Ltd. (F), Nidek Co., Ltd. (F), Nidek Co., Ltd. (P), Novartis Pharmaceutical Co., Ltd. (F), Otsuka Pharmaceutical Co., Ltd. (F), Santen Pharmaceutical Co., Ltd. (F), SEED Co., Ltd. (F), SEED Co., Ltd. (P), Senju Pharmaceutical Co., Ltd. (F), Senju Pharmaceutical Co., Ltd. (P), Takeyama Co., Ltd. (F), Wakamoto Pharmaceutical Co., Ltd. (F), White Medical Co., Ltd. (F)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 795. doi:https://doi.org/
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      Keitaro Hase, Kenichi Namba, Nobuyoshi Kitaichi, Daiju Iwata, Hyuma Tsuji, Haruka Wada, Ken-ichiro Seino, Susumu Ishida; Induced pluripotent stem cells-derived suppressor cells ameliorate experimental autoimmune uveoretinitis in mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):795. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Induced pluripotent stem cells-derived suppressor cells (iPS-SCs) have been known to have immunosuppressive ability in mice. In this study, we evaluate the efficacy of iPS-SCs in experimental autoimmune uveoretinitis (EAU) in mice.

Methods : iPS cells were established from spleen B cells isolated from naïve C57BL/6 mice, then they were stimulated with cytokines (e.g. macrophage-colony-stimulating factor, granulocyte macrophage-colony- stimulating factor and interleukin-4) and lipopolysaccharide to be differentiated into iPS-SCs. Mice received iPS-SCs intraperitoneally 24 hours before EAU induction.To induce EAU, mice were immunized with human interphotoreceptor-binding protein derived peptide 1-20 emulsified with complete Freund’s adjuvant, and purified Bordetella pertussis toxin was injected intraperitoneally as an additional adjuvant. Clinical severity of EAU was assessed every 3 or 4 days. Eyes were enucleated 21 days after immunization to evaluate the histopathological severity. T cell proliferative response was examined in vitro. CD4+T cells were enriched from draining lymph nodes of immunized mice at day 9, and labeled with division-tracking dye (CellTrace™ Violet). After co-cultured with irradiated syngeneic spleen cells and antigens with or without iPS-SCs, proliferation of T cells was evaluated. Cytokine levels of tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ) were also quantified in culture supernatant.

Results : EAU was significantly milder on day 21 in iPS-SCs treated group (2.5 ± 0.5) than controls (1.6 ± 0.5, p < 0.05) clinically. Histologic score was lower in treated mice than in controls. T cell proliferative response was suppressed in the presence of iPS-SCs (17.6 ± 1.1%) compared with the controls (37.5 ± 0.6%, p < 0.01). The level of nitric oxide was significantly elevated when cultured with iPS-SCs (32.5 ± 4.5 μM) than controls (0.2 ± 0.2 μM, p < 0.01). In contrast, concentrations of TNF-α (iPS-SCs: 55.4 ± 3.2 pg/ml, control: 91.7 ± 2.5 pg/ml) and IFN-γ(iPS-SCs: 2508.7 ± 64.1 pg/ml, control: 4739.5 ± 117.5 pg/ml) were significantly decreased in the presence of iPS-SCs compared with the controls (p < 0.01).

Conclusions : The results of the present study indicated the possibility of the new “immunotherapy approach” to uveitis.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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