Mice deficient in NOX2 display severe thymic atrophy and lymphopenia in association with neutrophilic lung inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06446
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: Yokohama City University
• Principal Investigator: ARATANI Yasuaki 横浜市立大学, 理学部, 教授 (30192470)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 免疫 / 好中球 / 活性酸素

Outline of Final Research Achievements

Neutrophils and macrophages play a role in host defense against bacteria and fungi. Activated neutrophils generate superoxide anions and hypochlorous acid via phagocyte NADPH oxidase (NOX2) and myeloperoxidase (MPO), respectively. This study aimed to examine the role of these enzymes for the systemic inflammation. In a zymosan-induced inflammation model, NOX2-deficient (NOX2-KO) mice exhibited more severe thymic atrophy, lymphopenia, and more remarkable neutrophilic lung inflammation in association with accumulation of higher amounts of TNF-α and KC in NOX2-KO lungs. Strikingly, zymosan-stimulated NOX2-KO neutrophils produced a greater amount of TNF-α than wild-type neutrophils. NOX2-KO macrophages produced a greater amount of KC in response to zymosan. These results suggest that the greater TNF-α and KC production from the NOX2-KO phagocytes at least partly contributes to the accumulation of neutrophils observed in the lungs of these mutant mice.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

感染によって炎症が重篤化することは肺炎などでよく知られている。ところが、病原体が検出されないにも関わらず劇的なサイトカインストームを伴う重篤な炎症が進行することもあり、NOX2を欠損したヒトにおいてもそのような病態を時折発症することが知られている。しかし、その発症機構は不明なため治療法に乏しい。本研究は、原因不明の炎症性疾患発症における食細胞機能異常のリスクを知るという基礎研究としての意義がある。