Fig. 8

Proposed mechanism of PepN on CD11c^high macrophages-dependent anti-inflammatory effects in allergic asthma. In asthmatic mice, PepN promotes the proliferation of lung-resident CD11c^high macrophages in situ and stimulates the recruitment of BMDM to the respiratory tract and differentiation into CD11c^int macrophage cell pool. Evanescence of CD11c^int macrophages in PepN-treated mice was found to be phenotypical transformation into pulmonary CD11c^high macrophages. Furthermore, PepN-preprogramed CD11c^high macrophages acquired an anti-inflammatory property by shaping the metabolic preference of OXPHOS and upregulated the expression of costimulatory molecules to promote Treg differentiation, thus exerting a protective effect against asthmatic airway inflammation. Overall, our data suggest that the microbial component PepN is a potential prevention and treatment strategy for allergic asthma by targeting CD11c^high macrophages and this provides new theoretical foundation for the hygiene hypothesis