| Project/Area Number |
18K16142
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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 54020:Connective tissue disease and allergy-related
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| Research Institution | Fukushima Medical University (2019)
University of Yamanashi (2018) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 肥満 / I型アレルギー / マスト細胞 / 脂肪組織マクロファージ / IL-12 |
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| Outline of Final Research Achievements |
In this study, we investigate whether and how obesity exacerbates allergic reaction.
We found that increased plasma histamine level by passive systemic anaphylaxis, a classical model of IgE/mast cell-mediated systemic allergic reaction, was significantly higher in high fat diet-induced obese mice than non-obese mice. To elucidate how obesity reinforces allergic reaction, we focus on the roles of adipose tissue macrophages because they are closely associated with obesity-related chronic diseases. In vitro experiment revealed that mRNA expression of osteopontin in macrophages was up-regulated by co-culturing with adipocytes. It has been reported that osteopontin regulates IL-12 production. Indeed, we found that IL-12 significantly enhanced degranulation of mast cell by antigen-challenge.
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| Academic Significance and Societal Importance of the Research Achievements |
2型糖尿病などの肥満関連疾患の増加が世界中で問題となっており、近年では肥満が癌やアレルギーなどの発症・進展に寄与する可能性が示唆されているが、不明な点も多い。
本研究は、マウスを用いた個体レベルで肥満がアレルギーを悪化させることを明らかにした。またそのメカニズムとして脂肪組織局在マクロファージから産生されるオステオポンチンやIL-12がマスト細胞の脱顆粒反応を促進する可能性を示した。
今後、脂肪組織局在マクロファージや血漿IL-12などを標的とすることでアレルギーを始め多くの肥満関連疾患の治療戦略に繋がる可能性がある。
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