Amelioration of experimental autoimmune uveoretinitis with macrophage-like induced pluripotent stem cell-derived suppressor cells
| Project/Area Number |
16K11310
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Hokkaido University |
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Principal Investigator |
Namba Kenichi 北海道大学, 大学病院, 講師 (70333599)
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| Co-Investigator(Kenkyū-buntansha) |
清野 研一郎 北海道大学, 遺伝子病制御研究所, 教授 (20312845)
北市 伸義 北海道医療大学, 予防医療科学センター, 教授 (40431366)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | マクロファージ様免疫抑制性細胞 / マウス実験的自己免疫性ぶどう膜網膜炎 / 抗原特異的なCD4+T細胞 / iPS細胞 / 臨床スコア / 組織学的スコア / 実験的自己免疫性ぶどう膜網膜炎 / iPS 細胞 / iNOS / 眼免疫学 |
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| Outline of Final Research Achievements |
Macrophage-like induced pluripotent stem cells-derived suppressor cells (iPS-SCs) were induced from iPS cells derived from B cells enriched from mice spleen. The intraperitoneal administration of iPS-SCs significantly ameliorated experimental autoimmune uveoretinitis (EAU) induced by the immunization of human interphotoreceptor-binding protein derived peptide (hIRBPp) 1-20 in both clinical severity with funduscopy and histological severity with HE staining than controls. In vitro experiment, hIRBPp1-20 antigen specific CD4 positive cells enriched from draining lymph nodes of immunized mice, antigen presenting cells and hIRBPp1-20 were co-cultured with or without iPS-SCs. As a result, we found that iPS-SCs significantly suppressed T cell proliferative response.
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| Academic Significance and Societal Importance of the Research Achievements |
ぶどう膜炎の全身治療としてステロイド薬,、免疫抑制薬、生物学的製剤があるが、それらは根本的な治療ではないため減量中に炎症が再燃することや、有害事象が生じることが問題となる。一方、より有害事象が少ない可能性のある治療法として免疫療法があげられる。動物モデルマウスにおいて制御性T細胞や樹状細胞といった治療が試みられたが、誘導できる細胞数に限界があること、逆にぶどう膜炎を増悪させる細胞の混入・誘導の可能性があった。今回検討したiPS-SCsは、患者自身の細胞から誘導するため、拒絶反応を起こさない点や大量に作製できる可能性がある点で、有用性が高いことが期待できると考えられる。
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Report
(4 results)
Research Products
(53 results)
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[Journal Article] Choroidal thickening prior to anterior recurrence in patients with Vogt-Koyanagi-Harada disease.2016
Author(s)
Tagawa Y, Namba K, Mizuuchi K, Takemoto Y, Iwata D, Uno T, Fukuhara T, Hirooka K, Kitaichi N, Ohno S, Ishida S
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Journal Title
Br J Ophthalmol
Volume: 100
Issue: 4
Pages: 473-477
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Choroidal circulation impairment during the anterior recurrence of Vogt-Koyanagi-Harada disease confirmed with indocyanine green angiography and laser speckle flowgraphy.2016
Author(s)
Takemoto Y, Namba K, Uno T, Mizuuchi K, Iwata D, Ohno S, Hirooka K, Hashimoto Y, Saito W, Sugiyama K, Ishida S.
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Journal Title
Acta Ophthalmol.
Volume: 94
Issue: 7
Pages: 629-636
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Serum levels of epidermal growth factor receptor ligands in patients with non-infectious uveitis2018
Author(s)
Fukuhara T, Hamada S, Kitaichi N, Namba K, Kamimura D, Noda K, Kanda A, Iwata D, Mizuuchi K, Murakami M, Ohno S, Ishida S.
Organizer
18th International Conference on Behcet’s Disease
Related Report
Int'l Joint Research
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[Presentation] Epidemiology of severe, refractory, prolonged ocular sarcoidosis2018
Author(s)
Suzuki K, Namba K, Mizuuchi K, Iwata D, Fukuhara T, Hase K, Hamada S, Ohno S, Kitaichi N, Ishihara M, Ishida S.
Organizer
36th World Ophthalmology Congress (WOC) 2018
Related Report
Int'l Joint Research
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[Presentation] Serum levels of epidermal growth factor ligands in patients with uveitis. International Distinguished Paper2018
Author(s)
Kitaichi N, Hamada S, Namba K, Kamimura D, Noda K, Kanda A, Iwata D, Mizuuchi K, Fukuhara T, Murakami M, Ohno S, Ishida S
Organizer
フォーサム2018
Related Report
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