Development of a novel method to generate human iPS cell-derived dendritic cell progenitors and their effectiveness
| Project/Area Number |
19K09105
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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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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
善本 隆之 東京医科大学, 医学部, 教授 (80202406)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 樹状細胞 / 単球細胞株 / iPS細胞 / IL-27 / 単球 / 樹状細胞前駆細胞株 / iPS / 樹状細胞前駆細胞 |
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| Outline of Research at the Start |
樹状細胞（DC）は、最強の抗原提示能力を有する細胞で、がん抗原を取り込ませたDCを患者に戻すDCワクチン療法は、その治療効果が期待されている。一方、IL-10などの抑制性分子存在下で成熟DCを分化誘導すると、免疫寛容誘導性DCが誘導され、自己免疫病などへの治療応用が期待されている。ところが、患者末梢血から採取できるDC数には限界があり、ヒトDCを大量に効率的にin vitroで増やす技術の開発が望まれている。そこで、本研究では、サイトカイン刺激や遺伝子導入、低分子阻害剤処理などにより、ヒトDC前駆細胞を効率よく大量に増やす方法を確立し、その作用機序やがん治療応用への有効性を明らかにすることを目指す。
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| Outline of Final Research Achievements |
We aim at establishing a new method to efficiently generate human dendritic cell (DC) progenitors in large quantities and clarifying the effectiveness on application to various therapies. In the present study, we have obtained the results showing that IL-27 acts on human umbilical cord blood-derived CD34+ HSCs to generate DC progenitors similarly to acting on mouse HSCs as we reported previously. Moreover, human iPS-derived DC progenitors and human peripheral CD14+ monocytes transduced with genes related to cell survival and cell cycle were revealed to proliferate well, and the DCs differentiated from the proliferating monocytes showed high immune reactivity similar to primary DCs. Thus, these cells have great potential for application to therapies such as cancer, autoimmune diseases and allergy.
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| Academic Significance and Societal Importance of the Research Achievements |
樹状細胞（DC）は、最も強い抗原提示能力を有する細胞で、がん抗原を取り込ませたDCを患者に戻すDCワクチン療法は、その治療効果が期待されている。一方、IL-10などの抑制性分子存在下で成熟DCを分化誘導すると、免疫寛容誘導性DCが誘導され、自己免疫病などへの治療応用が期待されている。ところが、患者末梢血から採取できるDC数には限界があり、ヒトDCを大量に効率的にin vitroで増やす技術の開発が望まれている。本研究は、ヒトDC前駆細胞を効率よく大量に増やす方法を検討し、その成果はがんや自己免疫などの治療応用への有用な知見となることが期待される。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] A chaperone-like role for EBI3 in collaboration with calnexin under inflammatory conditions.2021
Author(s)
Watanabe A, Mizoguchi I, Hasegawa H, Katahira Y, Inoue S, Sakamoto E, Furusaka Y, Sekine A, Miyakawa S, Murakami F, Xu M, Yoneto T, Yoshimoto T.
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Journal Title
Front Immunol.
Volume: 12
Pages: 757669-757669
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Necroptosis of intestinal epithelial cells induces type 3 innate lymphoid cell-dependent lethal ileitis.2019
Author(s)
Shindo R, Ohmuraya M, Komazawa-Sakon S, Miyake S, Deguchi Y, Yamazaki S, Nishina T, Yoshimoto T, Kakuta S, Koike M, Uchiyama Y, Konishi H, Kiyama H, Mikami T, Moriwaki K, Araki K, Nakano H.
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Journal Title
iScience
Volume: 15
Pages: 536-551
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Plasmacytoid dendritic cells protect against immune-mediated acute liver injury via IL-35.2019
Author(s)
Koda Y, Nakamoto N, Chu P, Ugamura A, Teratani T, Shiba S, Taniki N, Sujino T, Miyamoto K, Mikami Y, Suzuki T, Yamaguchi A, Morikawa R, Sato K, Yoshimoto T, Kanai K.
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Journal Title
J Clin Invest
Volume: 129(8)
Issue: 8
Pages: 3201-3213
DOI
Related Report
Peer Reviewed / Open Access
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