Fas/Fas Ligand–mediated Apoptosis Promotes Hypersensitivity Pneumonitis in Mice by Enhancing Maturation of Dendritic Cells

Rationale: Fas/Fas ligand (FasL)-mediated apoptosis has been implicated in various lung diseases, but whether Fas/FasL-mediated apoptosis in the lungs plays a critical role in the development of hypersensitivity pneumonitis (HP) is unclear.Objectives: To explore the functional roles of Fas/FasL-mediated apoptosis in HP.Methods: Fas-deficient (lpr/lpr), FasL-deficient (gld/gld), and B6 mice were challenged with Saccharopolyspora rectivirgula (SR) antigen intranasally.Measurements and Main Results: lpr/lpr and gld/gld mice exhibited attenuation of HP in terms of histological alterations, influx of immune cells in bronchoalveolar lavage fluid (BALF), and SR-specific immune responses compared with B6 mice, similar to the effects of SR in B6 mice given a caspase inhibitor. The lungs of lpr/lpr and gld/gld mice showed high IL-4 production and low IFN-γ, IL-8, macrophage inflammatory protein-2, IL-1β, and tumor necrosis factor-α production compared with those of B6 mice. Moreover, mice with chimeric B6 and lpr/l...