sST2 is an important molecule in neutrophilic asthma: as a biomarker and a target for treatment

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09628
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kyorin University
• Principal Investigator: Watanabe Masato 杏林大学, 医学部, 学内講師 (00458902)
• Co-Investigator(Kenkyū-buntansha): 皿谷 健 杏林大学, 医学部, 准教授 (40549185) ; 滝澤 始 杏林大学, 医学部, 教授 (80171578) ; 田村 仁樹 杏林大学, 医学部, 助教 (80616607) ; 本多 紘二郎 杏林大学, 医学部, 助教 (20802995)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 喘息 / 好中球 / IL-33 / sST2 / ST2

Outline of Final Research Achievements

Neutrophilic asthma, characterized by neutrophil accumulation in the airways, is the most severe phenotype of asthma; thus, a strategy for controlling airway neutrophilia is desired to treat patients with severe asthma. We previously reported that sST2, a decoy receptor for IL-33, is associated with neutrophilic airway disease. Here, we hypothesized that sST2 plays a crucial role in pathogenesis of neutrophilic asthma. To address this, we conducted a clinical study assessing sputum and breath condensate from asthmatics and in vitro experiments using bronchial epithelial cells. We discovered that IL-33 facilitates airway neutrophilia, and that sST2 is an intrinsic regulator that ameliorates IL-33-related airway inflammation.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

我々は、喘息患者の喀痰や呼気の解析と気管支上皮細胞の培養実験を組み合わせたトランスレーショナルリサーチを行った。その結果、喫煙、酸化ストレス、および好中球エラスターゼが気管支上皮細胞でIL-33の発現と放出を促進することと、IL-33は気管支上皮細胞のサイトカイン産生を増強して好中球性炎症を惹起することを発見した。sST2は重症喘息のバイオマーカーであるが、生理的な意義は抗炎症作用であった。我々の成果は、sST2補充療法が重症喘息の新規治療戦略になり得ることを示している。