ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1663513
This article is part of the Research TopicSentinels of the Immune System: Tissue-Resident Macrophages in the Battle Against Infection and AutoimmunityView all 4 articles
TNF-α-mediated downregulation of CD36 and phagocytic impairment of alveolar macrophages via upregulation of ADAM17 in Asthma
Provisionally accepted
Xingyue Liu
Ya Li
Feifei ShangMinzhu NiuJiaqi YanMinyu XieXiangnan Tao
Han Huang
Wenwen WuShu Dong
Yingzi Chen
Fan WuShujun GuoYulin DuMengqing HuaYanmei Hao*Chuanwang Song*- Bengbu Medical University, Bengbu, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Alveolar macrophages (AMs) are specialized phagocytes in the airways that play a crucial role in maintaining bronchoalveolar homeostasis through phagocytosis, the clearance of apoptotic cells. However, the characteristics and molecular mechanisms of AMs-mediated phagocytosis during the pathogenesis of asthma remain poorly characterized. Methods: An ovalbumin (OVA)-induced asthma model was established in mice through intraperitoneal sensitization followed by intranasal challenge. AMs were isolated from the bronchoalveolar lavage fluid of control and OVA-induced mice using adherence-based purification. The phagocytic capacity of AMs, as well as the expression levels of CD36 and ADAM17, were quantified by flow cytometry. Results: A significant reduction in both phagocytic efficiency and CD36 expression was found in the AMs of OVA-induced mice compared to control mice. Blockade of CD36 resulted in a marked decline in the phagocytic efficiency of normal AMs. Expression of ADAM17 was found to be notably elevated on the surface of AMs from OVA-induced mice compared to controls. Knockdown of ADAM17 led to a substantial increase in CD36 expression and a corresponding increase in phagocytic efficiency. Stimulation with tumor necrosis factor-α (TNF-α) resulted in a significant upregulation in ADAM17 and marked downregulation in CD36 expression levels, as well as impaired the phagocytic efficiency of AMs. Importantly, ADAM17 knockdown attenuated the TNF-α-mediated downregulation of CD36 expression and the associated impairment of phagocytic capacity in AMs. Conclusion: AMs from OVA-induced mice displayed significantly impaired phagocytic capacity. Airway TNF-α upregulated ADAM17, which in turn downregulated CD36 expression on AMs, ultimately suppressing their phagocytic function.
Keywords: Asthma, alveolar macrophages, Phagocytosis, CD36, ADAM17, TNF-α
Received: 10 Jul 2025; Accepted: 02 Oct 2025.
Copyright: © 2025 Liu, Li, Shang, Niu, Yan, Xie, Tao, Huang, Wu, Dong, Chen, Wu, Guo, Du, Hua, Hao and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yanmei Hao, 1036835322@qq.com
Chuanwang Song, bbmu127@outlook.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.