| Project/Area Number |
17K15718
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Yamazumi Yusuke 東京大学, 定量生命科学研究所, 特任助教 (40773768)
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| Research Collaborator |
Sasaki Oh
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 喘息 / 気道炎症 / 好中球 / アレルギー・免疫関連疾患 |
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| Outline of Final Research Achievements |
It has recently been shown that in a subgroup of severe asthma cases, neutrophils that infiltrate into the airways play an important role in inflammation. However, the mechanisms underlying this increased neutrophil infiltration are not well understood. Here, using a mouse model of steroid-resistant neutrophilic inflammation, we show that mice deficient for the RNA-binding protein Mex-3B have significantly less neutrophil infiltration in the airways than wild-type mice. We further demonstrate that Mex-3B post-transcriptionally upregulates CXCL2, a chemokine that induces neutrophil chemotaxis and migration. Moreover, we show that treatment with either anti-CXCL2 antibody or anti-Mex-3B antisense oligonucleotide suppresses neutrophilic allergic airway inflammation. These results suggest that Mex-3B-mediated induction of CXCL2 is crucial for steroid-resistant neutrophilic allergic airway inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
重症喘息とは、既存薬が効きにくい重篤な喘息のことである。重症喘息の患者数は喘息患者全体の10%程度にも関わらず、喘息で亡くなる患者の30-50%をも占める。重症喘息の病態は人によって大きく異なっているため、その発症メカニズムには未だ不明な点が多い。本研究により、CXCL2やMex-3Bの阻害によって、重症喘息の症状が緩和されることが明らかになった。本研究成果により、重症喘息に対する創薬研究の新たな展開が期待される。
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