| Project/Area Number |
17K08791
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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 |
Experimental pathology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 雅 北里大学, 医学部, 講師 (40611843)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | NKT細胞 / 実験的自己免疫性心筋炎 / マウス / α-ガラクトシルセラミド / 心マクロファージ / リモデリング / 線維化 / 炎症制御 / CD1d / 抗原提示細胞 / 抗炎症作用 / NKT細胞リガンド / 疾患モデル / マクロファージ / 抗炎症性作用 / 実験病理学 / 心筋リモデリング |
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| Outline of Final Research Achievements |
iNKT cell, as an innate subset of T cells, exhibits various function and plays a regulatory role in some inflammatory diseases. In the present study, I employed a model of experimental autoimmune myocarditis (EAMC) by sensitizing BALB/c mice with MyHC-α peptides + complete Freund adjuvant (CFA) and demonstrated; 1) EAMC was aggravated in TRAJ18-/- mice in BALB/c background where iNKT-cell is deficient, 2) fibrotic lesion area was reduced in BALB/c mice when sensitized with MyHC-α + CFA emulsion including α-GC, 3) cardiac macrophage (CX3CR1+, CD206+, MerTK+, class II MHC+) is thought to be a candidate as ligand-presenting cell for iNKT cell. In case of myocarditis, as one of the causes for heart failure, iNKT cells accumulated in the heart in inflammatory condition exhibit protective role by reducing production of inflammatory cytokines, such as TNF-α.
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| Academic Significance and Societal Importance of the Research Achievements |
心疾患と続発する心不全は国民の死因の第２位を占め，予防法やより効果的な治療法の開発は喫緊の課題である。心不全の原因の１つである心筋炎症時に、心臓に集積したiNKT細胞はリガンドによる活性化を行うことにより、炎症性サイトカイン産生抑制を介して心筋防護効果を発揮することを明らかに出来た。抗炎症性効果をリガンド投与時期を予防的投与から治療的投与に展開出来れば実用化に希望が繋げる。
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