Fcγ Receptors Modulate Pulmonary Inflammation by Activating Innate Immune Cells in Murine Hypersensitivity Pneumonitis

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled particulate antigens. The family of Fcγ receptors (FcγRs) has emerged as central regulators for modulating both pro-and anti-inflammatory responses. However, the role of FcγRs in the development of HP has not been investigated yet. METHODS: To explore the functional roles of FcγRs in HP, FcγR(-/-) and B6 mice were challenged with Saccharopolyspora rectivirgula (SR) antigen intranasally, and compared these mice in terms of the histological change, infiltrated immune cells in BALF and in vitro immune responses. RESULTS: FcγR(-/-) mice exhibited attenuation of HP in terms of histological alterations, and reduced numbers of neutrophils and macrophages in and the increased CD4:CD8 ratio of bronchoalveolar lavage fluid. The lungs of FcγR(-/-) mice showed high production of Th2 cytokine such as IL-4 and slightly low production of Th1 cytokine, INF-γ compared to those of B6 mice. However, SR-specific adaptive immune responses of FcγR(-/-) mice were similar to those of B6 mice. CONCLUSION: These results demonstrate that activating Fcγ receptors play an important role in activating neutrophils and macrophages in pulmonary inflammation and inducing Th1 differentiation by regulating cytokine expression in SR-induced HP.