Role of LILRB4 for the pathogenesis of COPD
| Project/Area Number |
18K15914
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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 53030:Respiratory medicine-related
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| Research Institution | Tohoku University |
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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: ¥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 | COPD |
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| Outline of Final Research Achievements |
Leukocyte immunoglobulin-like receptor B4 (LILRB4) is one of the inhibitory receptors in myeloid cells. LILRB4 has been described as highly expressed in lung, but little is known about its association with respiratory diseases. We aimed to elucidate the role of LILRB4 in the pathogenesis of COPD using resected lung specimens and a mouse emphysema model.LILRB4-positive interstitial macrophages were increased in COPD patients compared to non-COPD smokers (p = 0.018). The level of LILRB4 expression was correlated with the severity of emphysematous lesions (rs = 0.559, p < 0.001), whereas the amount of smoking showed no correlation with LILRB4 expression. Increased LILRB4 on interstitial macrophages was also observed in elastase-treated mice (p = 0.008). LILRB4-deficient mice showed severer emphysematous lesions with increased MMP-12 expression in the model.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、ヒト間質マクロファージのLILRB4発現がCOPD発症と重症度に関連していた。エラスターゼマウスモデルを用いた実験で、LILRB4陰性間質マクロファージではMMP-12のmRNA発現が亢進すること、またMMP-12の主要な産生細胞は間質マクロファージであるため、LILRB4欠損マウスではMMP-12産生が増加して気腫形成が増悪することを確認した。LILRB4発現間質マクロファージの研究がCOPDの病態解明と新規治療基盤の解明に繋がると考える。
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Report
(3 results)
Research Products
(4 results)
