Study on the mechanism(s) of immunosenescence and its application for vaccine development.
| Project/Area Number |
26450443
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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 |
Integrative animal science
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
福島 祐二 京都大学, 医学研究科, 研究員 (90583146)
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| Co-Investigator(Renkei-kenkyūsha) |
MASHIMO Tomoji 大阪大学, 大学院医学研究科, 准教授 (80397554)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 免疫老化 / T細胞 / PD-1 / CD153 / オステオポンチン / 全身性エリテマトーデス / 死細胞処理 / 貪食 / 自己免疫疾患 / 自己抗体 / 老化関連T細胞 / 胚中心 / miR181a |
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| Outline of Final Research Achievements |
Immune aging results in diminished adaptive immunity and increased risk for autoimmunity. We previously discovered a unique T cell population that increases with age, termed senescence-associated (SA-) T cells. The SA-T cells secret abundant osteopontin (OPN) in respond to auto B cells. Here, we demonstrate that OPN secreted by SA-T cells, which selectively accumulate in the germinal centers (GCs) of lupus-prone mice, interferes with phagocytosis of apoptotic cells. OPN induced diffuse and prolonged Rac1 activation in phagocytes via integrin alpha v beta 3 and inhibited the dissolution of phagocytic actin cup, causing defective apoptotic cell engulfment. Our results suggest that OPN secreted by follicular SA-T cells in GCs promotes a continuous supply of intracellular autoantigens via apoptotic cells, thus playing a key role in the progression of the autoreactive GC reaction and leading to pathogenic autoantibody production in lupus-prone mice.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Osteopontin in spontaneous germinal centers inhibits apoptotic cell engulfment and promotes autoantibody production in lupus mice.2016
Author(s)
Sakamoto、K., Fukushima、Y., Itoh、K., Matsuda, M., Nagata, S., Minato, N., and Hattori, M.
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Journal Title
J. Immunol.
Volume: 197
Issue: 6
Pages: 2177-2186
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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