2023 Fiscal Year Final Research Report
Pathophysiology of pulmonary nontuberculous mycobacterial infections focusing on abnormal accumulation of mucin
| Project/Area Number |
21KK0148
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
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| Research Institution | Keio University |
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Principal Investigator |
ASAKURA TAKANORI 慶應義塾大学, 医学部(信濃町), 共同研究員 (10645609)
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| Co-Investigator(Kenkyū-buntansha) |
長谷川 直樹 慶應義塾大学, 医学部(信濃町), 教授 (20198724)
上蓑 義典 慶應義塾大学, 医学部(信濃町), 講師 (60748789)
南宮 湖 慶應義塾大学, 医学部(信濃町), 講師 (50594644)
西村 知泰 慶應義塾大学, 保健管理センター(日吉), 准教授 (90348649)
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| Project Period (FY) |
2021-10-07 – 2024-03-31
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| Keywords | 気管支拡張症 / 肺非結核性抗酸菌(NTM)症 / 肺MAC症 / 分泌型ムチン / MUC5B / IL1経路 / 末梢気道/細気管支 / CRISPR-Cas9 |
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| Outline of Final Research Achievements |
Lung histopathology specimens from NCFB lungs (including pre-existing non-tuberculous Mycobacterium tuberculosis infection) and normal lungs in Japan and the United States were evaluated. Both proximal and distal bronchioles of diseased lungs were rich in mucus plugs, and both MUC5B and MUC5AC were elevated in proximal bronchioles, whereas MUC5B was selectively elevated in distal bronchioles. MUC5B and MUC5AC were significantly elevated in primary human airway epithelial cells stimulated with sputum-derived supernatants from NCFB patients and were decreased by IL1R1 knockout. We also confirmed that mucin levels are elevated in pulmonary NTM disease and sputum samples and strongly correlate with IL1B levels, and proteomic analysis showed that peripheral airway-specific markers are elevated in pulmonary NTM disease.
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| Free Research Field |
呼吸器感染症、呼吸器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
気管支拡張症(NCFB)における病変の主座が末梢気道(細気管支)にあり、同部位における粘液貯留が重要であることを世界で初めて示した。さらに、NCFBに対するIL-1経路に対する治療薬は、NCFBの粘液閉塞と肺傷害を改善する可能性を明らかにした。
NCFBの発症と進行に関する今後の研究には近位・遠位細気管支を共に含むことが重要である。今後、①細気管支病変が注目されている喘息・慢性閉塞性肺疾患、CFや原発性線毛機能不全症などの他の気管支拡張症との比較、②気道上皮、粘液栓、粘膜下組織などの各種細胞、病原微生物を含む相互作用を探索する上で重要な分子基盤を明らかにした。
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