ATP6V0d2 Suppresses Alveoli Macrophage Alternative Polarization and Allergic Asthma via Degradation of PU.1

• Published in: Allergy, asthma & immunology research Vol. 13; no. 3; pp. 479 - 497
• Main Authors: Liu, Na, Feng, Yuchen, Liu, Huicheng, Wu, Wenliang, Liang, Yuxia, Li, Pingfei, Wei, Zhengping, Wu, Min, Tang, Zhao-Hui, Han, Junyan, Cheng, Xiang, Liu, Zheng, Laurence, Arian, Li, Huabin, Zhen, Guohua, Yang, Xiang-Ping
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Academy of Asthma, Allergy and Clinical Immunology 01.05.2021; The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
• Subjects: Adenosine triphosphatase; Allergens; Alveoli; Asthma; CCL17 protein; Degradation; Inflammation; Lysosomes; Macrophages; Model testing; Molecular modelling; Original; Ovalbumin; Pathogenesis; Polarization; PU.1 protein; Regulators; Respiratory tract diseases; Sputum; V-type ATPase; alveolar macrophage; Pu.1 protein; Asthma
• ISSN: 2092-7355; 2092-7363
• DOI: 10.4168/aair.2021.13.3.479

Macrophages are important regulators of environmental allergen-induced airway inflammation and asthma. ATP6V0d2 is a subunit of vacuolar ATPase highly expressed in macrophages. However, the functions of ATP6V0d2 in the regulation of pathogenesis of allergic asthma remain unclear. The aim of this study is to determine the function and related molecular mechanisms of macrophage protein ATP6V0d2 in allergic asthma. We compared the disease severity between female C57BL/6 wild-type and mice in an ovalbumin (OVA)-induced asthma model. We also investigated the association of expression of , and with disease severity among asthmatic patients. The expression of in sputum cells of asthmatic patients and in the lungs of OVA-challenged mice was enhanced compared to healthy subjects and their counterparts, respectively. However, -deficient mice exaggerated inflammatory cell infiltration as well as enhanced alternative activated macrophage (AAM) polarization and mucus production in an OVA-induced asthma model. Furthermore, we found that Atp6v0d2 promoted lysosomal degradation of Pu.1, which induced AAM polarization and Ccl17 production. Among asthma patients, expression was inversely associated with disease severity, whereas and expression was positively associated with disease severity. Our results identify macrophage Atp6v0d2, as an induced feedback inhibitor of asthma disease severity by promoting Pu.1 lysosomal degradation, which may in turn leads to reduced AAM polarization and Ccl17 production.