Elucidation of cellular and molecular mechanisms underlying the regulation of lung inflammation in acute respiratory distress syndrome (ARDS)

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K18255
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Karasuyama Hajime 東京医科歯科大学, 高等研究院, 特別栄誉教授 (60195013)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 急性呼吸窮迫症候群 / 呼吸不全 / 炎症寛解 / 好塩基球 / 好中球 / サイトカイン / 遺伝子改変マウス / １細胞トランスクリプトーム解析

Outline of Final Research Achievements

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute respiratory failure with a high mortality rate and no effective pharmacological therapies. While recent human cohort studies implied the correlation between the severity of ARDS and the paucity of blood basophils, the causative relationship between them remains elusive. The present study clarified that basophils play a crucial role in the resolution of a mouse model of ARDS through the production of cytokine IL-4 which in turn acts on neutrophils to suppress their expression of anti-apoptotic genes and pro-inflammatory mediators and therefore restrict lung inflammation.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

ARDSは重症肺炎（コロナウイルス肺炎など）、敗血症、外傷や誤嚥などが誘因になって発症する重篤な肺疾患で、呼吸不全に対して人工呼吸管理が行われるがARDSを直接改善する特効薬は無く、新規治療法の開発が切望されている。本研究におけるARDSマウスモデルの解析結果を踏まえて、さらにヒトARDS病態における好塩基球ならびにサイトカインIL-4の役割を解析することで、ARDS新規治療法の標的が明らかになるものと期待される。