Loss of Rab44 attenuates ovalbumin-induced allergic airway inflammation by modulating immune responses and eosinophil function.

Introduction: Asthma is a chronic inflammatory disease of the airways accompanied by mucus hypersecretion, airway remodeling, and bronchial hyperresponsiveness. However, the mechanisms by which membrane trafficking molecules contribute to the development of asthma remain unclear. In the present study, we investigated the role of Rab44 in a murine model of allergic airway inflammation mimicking human asthma, as we previously identified Rab44 and are exploring its function. Methods: Experimental allergic airway inflammation was induced in Rab44-knockout (KO) and wild type (WT) mice sensitized to ovalbumin (OVA). Histopathological analysis, RNA sequencing (RNA-seq) analysis, degranulation assays, adhesion and migration assays, and flow cytometric analysis of adhesion and chemokine receptors were performed. Results: Compared with WT mice, Rab44-KO mice exhibited impaired OVA-induced allergic airway inflammation. RNA-seq analysis revealed that Rab44 deficiency affected several signaling pathways involved in immune and inflammatory responses in the lungs of OVA-induced mice. Moreover, the mRNA levels of cytokines and the numbers of lymphocytes, monocytes, and eosinophils infiltrating the bronchoalveolar lavage fluid were decreased in KO mice compared with WT mice. In cultures of eosinophils derived from bone marrow cells, Rab44-KO eosinophils exhibited aberrant differentiation and impaired release of eosinophil peroxidase but not major basic protein. Rab44-KO eosinophils exhibited reduced cell adhesion and chemotaxis. Consistent with these findings, Rab44-KO eosinophils showed impaired surface expression of adhesion and chemokine receptors. Conclusion: These results indicate that Rab44 deficiency attenuates OVA-induced allergic airway inflammation by modulating immune responses and eosinophil function.