Mechanisms of age-related changes in type 2 immune responses against nematode parasites in murine small intestine
| Project/Area Number |
16K08075
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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 | Miyagi University |
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Principal Investigator |
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| Research Collaborator |
Takai Toshiyuki
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 免疫老化 / 線虫感染 / Th2応答 / NMN / PD-1 / 腸内細菌 / 加齢 / サーチュイン / NAD / 線虫 / ＮＡＤ / サイトカイン / 2型免疫応答 / 免疫学 / 寄生虫 |
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| Outline of Final Research Achievements |
We investigated primary responses of aged mice against Heligmosomoides polygyrus, a gastrointestinal nematode parasite. Gene expression of Th2 cytokines in the small intestine remained at uninfected levels in aged mice but significantly increased in young mice. Alterations in Th2 immune responses in aged mice might be due to inappropriate or insufficient activation of CD4+ T cells in the submucosa. We focused on one of the inhibitory molecules, programmed death 1 (PD-1). FACS analysis revealed that the ratio of PD-1+CD25+ cells was significantly higher in aged mice. Next, we examined gene expression of sirtuin, a well-known molecule against aging, in relation to Th2 cytokines. There was a significant correlation with regard to IL-4 and IL-13; a higher sirtuin expression was associated with a higher Th2 cytokine expression. In conclusion, the expression of PD-1 and sirtuin are important for appropriate activation of CD4+ T cells against nematode infection in aged mice.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトや動物の健康を考えるとき、「ライフステージ」の視点は重要である。加齢期のさまざまな疾患に、免疫系の老化が関与する。寄生虫感染に対する宿主の防御応答も、加齢による影響を受けると考えられるが、詳細は明らかになっていない。ヒトの場合、寄生虫感染症は世界中で１０億人以上が感染し、年間２５０万人が死亡する。家畜・愛玩動物においてもヒト以上に身近な感染症であり、オーナーにとっては経済的負担・損失も大きい。本研究の成果により、消化管の免疫老化の機序について得られた知見は、寄生虫感染症だけでなく、サイトカインのアンバランスがもたらす様々な疾患の予防治療にも有用な知見となると考えられる。
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Report
(4 results)
Research Products
(13 results)
