| Project/Area Number |
18K17359
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 58020:Hygiene and public health-related: including laboratory approach
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
Takamasa Kido 東京慈恵会医科大学, 医学部, 講師 (40633152)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 亜鉛 / T細胞 / マクロファージ / 炎症反応 / 脾臓 / 亜鉛欠乏 / Th2細胞 / M2マクロファージ / 溶血性貧血 / 脾腫 / 末梢血 / 好中球 / interleukin (IL)-4 / 免疫 / Tリンパ球 / GATA-binding protein 3 / interleukin-4 / 免疫毒性 |
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| Outline of Final Research Achievements |
Zinc deficiency leads to immune dysfunction and aggravated inflammation, caused by an imbalance in the T-lymphocyte-macrophage pathway. In this study, the relationship between macrophage subtypes (M1 and M2) and helper T lymphocytes (Th1 and Th2) was examined using spleens from rats fed standard diet or a zinc-deficient, the latter with or without interleukin (IL)-4 injection or with return to a standard diet. The zinc-deficient diet led to significant decreases in IL-4/IL-13 mRNA expression, GATA-3 protein levels, M2 macrophages, CD3+ CD8+ cells, and IL-4/IL-13-positive cells, as well as significant increases in the inflammatory cytokine IL-1β and chemokine MIP-1α, indicating that zinc deficiency-induced aggravation of inflammation is Th2-related and is associated with loss of GATA-3, IL-4, and anti-inflammatory M2 macrophages. Importantly, IL-4 injection or dietary zinc supplementation recovered the effects of zinc deficiency on immune function.
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| Academic Significance and Societal Importance of the Research Achievements |
亜鉛欠乏は潜在的国民病として成人のみならず、高齢者に多い。そして、免疫機能が低下している高齢者では肺炎などの感染性疾患による罹患率が高値となっており、亜鉛欠乏が一要因として感染性疾患の炎症反応を悪化させていると推察できる。しかし、亜鉛欠乏と免疫機能への影響はこれまで断片的にしか明らかとさていなかった。
我々の基礎的研究において、亜鉛欠乏は免疫担当細胞に対して機能不全をもたらすことを明らかにし、亜鉛欠乏に伴う免疫機能の低下を介した炎症反応のメカニズムを解明した。
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