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

Na Liu1,2, Yuchen Feng3, Huicheng Liu1

  • 1Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China.

Abstract

Insights

Macrophage ATP6V0d2 acts as a protective factor in asthma by reducing inflammation and mucus. Its deficiency worsens allergic asthma symptoms, highlighting its role in regulating airway inflammation.

Area of Science:

  • Immunology
  • Respiratory Medicine
  • Molecular Biology

Background:

  • Macrophages play a key role in allergic asthma pathogenesis.
  • ATP6V0d2, a vacuolar ATPase subunit, is highly expressed in macrophages, but its function in asthma is unknown.

Purpose of the Study:

  • To investigate the role and molecular mechanisms of macrophage ATP6V0d2 in allergic asthma.
  • To determine if ATP6V0d2 influences airway inflammation, macrophage polarization, and mucus production.

Main Methods:

  • Comparison of disease severity in wild-type versus ATP6V0d2-deficient mice using an ovalbumin-induced asthma model.
  • Analysis of ATP6V0d2, PU.1, and CCL17 expression in asthmatic patients and mouse models.

Main Results:

  • ATP6V0d2 expression was elevated in asthmatic patients and OVA-challenged mice.
  • ATP6V0d2 deficiency exacerbated inflammation, alternative activated macrophage (AAM) polarization, and mucus production in asthma models.
  • ATP6V0d2 promotes lysosomal degradation of PU.1, reducing AAM polarization and CCL17 production.

Conclusions:

  • Macrophage ATP6V0d2 acts as an induced feedback inhibitor of asthma severity.
  • ATP6V0d2 reduces asthma severity by promoting PU.1 degradation, leading to decreased AAM polarization and CCL17 production.

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