Elucidate the refractory mechanism for obese asthma and its therapeutic targets.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17632
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SUZUKI YUZO 浜松医科大学, 医学部, 助教 (00758435)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肥満喘息 / オートファジー / 気道上皮 / TSLP / IL-33

Outline of Final Research Achievements

The present study revealed the importance of autophagy in obese asthma. The obese asthma model was created by high-fat diet and HDM sensitization. House dust mite (HDM)-sensitized Atg5-/- obese mice exhibited marked eosinophilic inflammation and airway hyper-reactivity (AHR), compared to wild-type (WT) obese mice. Analyses of Atg5-/- obese mice showed increased levels of Th2 cells but not ILC2s together with elevated expression of Th2 cytokines in the lung. The genetic analyses of epithelial cells from HDM-immunized Atg5-/- obesity-induced mice showed an elevated expression of TSLP (thymic stromal lymphopoietin) and IL33. Notably, HDM-sensitized Atg5-/- mice developed TSLP- and IL33-dependent eosinophilic inflammation and AHR. Our results suggest that autophagy contributes to the exacerbation of eosinophilic inflammation in obese asthma. Modulations of autophagy may be a therapeutic target in obesity-associated asthma.

Free Research Field

呼吸器病学

Academic Significance and Societal Importance of the Research Achievements

肥満の増加は，小児や成人に関わらず，世界的な健康課題である．肥満は喘息患者にも高頻度に見られ，重症喘息の中でも肥満喘息は最もコントロールが難しい一群である．しかし肥満喘息の難治化要因や，病態は十分に解明されていない．
本研究により，肥満にオートファジー低下が加わることが肥満喘息の病態や増悪に関わっていることが示された．そのためオートファジー制御が，今後の肥満喘息の新しい治療につながると考えられた．