The impact of Trem2-mediated macrophage polarization on the mechanisms of allergic rhinitis

Abstract

The study aimed to investigate the impact of Trem2-mediated macrophage polarization on the pathogenesis of allergic rhinitis (AR), with a focus on how Trem2 influences macrophage polarization and its downstream effects on nasal epithelial cells and eosinophil activity. A series of in vivo and in vitro experiments were conducted using C57BL/6J mice and primary macrophages. Mice were sensitized and challenged with ovalbumin (OVA) to induce AR, and various experimental groups were treated with or without Bacillus Calmette–Guérin (BCG) vaccine and Trem2 gene manipulation. Macrophage-specific Trem2 knockout mice (Trem2-cko) were used to assess the role of Trem2 in macrophage polarization and allergic inflammation. Flow cytometry, ELISA, qRT-PCR, histological staining, and immunohistochemistry were performed to analyze macrophage polarization, cytokine levels, epithelial cell proliferation, and eosinophil activity. The BCG vaccine effectively reduced inflammation in OVA-induced AR mice, significantly downregulating Trem2 expression in macrophages, which corresponded with reduced epithelial damage and mucus secretion. Trem2 deletion in macrophages enhanced the M1 polarization, resulting in greater anti-inflammatory effects following BCG treatment. In vitro studies showed that Trem2 overexpression in M2-polarized macrophages inhibited nasal epithelial cell proliferation and survival, whereas Trem2 silencing restored these functions. Furthermore, Trem2 promoted M2 polarization and enhanced eosinophil survival and proliferation, further exacerbating allergic inflammation. The regulation of these processes by Trem2 was mediated through DAP10 and DAP12 signaling pathways, which modulated macrophage polarization and eosinophil activity. Trem2-mediated macrophage polarization plays a crucial role in exacerbating allergic inflammation in AR by promoting M2 polarization and enhancing eosinophil function. The findings suggest that targeting Trem2 or its signaling pathways, particularly through DAP10 and DAP12, could offer novel therapeutic strategies for managing allergic rhinitis.