Production of M-CSF by human eosinophils

• Project/Area Number: 18K08421
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Matsumoro Kenji 国立研究開発法人国立成育医療研究センター, 免疫アレルギー・感染研究部, 部長 (60181765)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 好酸球 / サイトカイン / 気管支喘息 / マクロファージ / リモデリング / M-CSF / 組織リモデリング / ２型炎症

Outline of Final Research Achievements

The most important unmet need in the treatment of bronchial asthma is to elucidate the whole mechanisms of airway remodeling that induce irreversible respiratory function decline and to develop methods to prevent it. Eosinophils isolated from human peripheral blood showed a production and release of M-CSF in the supernatant upon exposure to immobilized secretory IgA, and an increase in M-CSF concentration in cell lysates upon IL-5 or GM-CSF stimulation. In addition, there was a significant correlation between the concentration of M-CSF and EDN, an eosinophil granule protein, in bronchoalveolar lavage fluid from patients with bronchial asthma and control disease. These results indicate that human eosinophils produce M-CSF, a cytokine essential for the differentiation of macrophages involved in the remodeling of bronchial asthma.

Academic Significance and Societal Importance of the Research Achievements

好酸球はアレルギー疾患や寄生虫感染時の免疫応答に中心的な役割を演じる白血球である。今回、好酸球が気管支喘息の病態を模した刺激によって、肺の線維化などの重篤な長期合併症である気道リモデリングに重要な役割を演じるマクロファージという別の白血球の分化を促進する蛋白（M-CSF）を産生することを新たに見いだした。また、実際に気管支喘息や他の肺疾患の患者さんの肺の洗浄液からこのM-CSFが好酸球の活性化指標と相関することを確認した。