Chemokine production during hypersensitivity pneumonitis

Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled particulate antigens. Individuals with HP develop lymphocytic alveolitis, granuloma formation, and fibrosis. HP is categorized as a Th1 disease, and granuloma formation is dependent on T cells and the Th1 cytokine IFN-gamma. We therefore hypothesized that the IFN-gamma-inducible chemokines IP-10, Mig, and I-TAC, which are frequently associated with Th1 diseases, would play an important role in the pathogenesis of disease. We analyzed the expression of multiple chemokines in the lungs of wild-type (WT) and IFN-gamma-knockout (GKO) mice exposed to the particulate antigen Saccharopolyspora rectivirgula (SIR). Our results demonstrate the production of IP-10, Mig, and I-TAC in WT mice during the development of HP, whereas GKO mice have reduced levels of IP-10 and no Mig or I-TAC mRNA in the lungs in response to SR exposure. The production of these chemokines is associated with an influx of CXCR3(+)/CD4(+) T cells into lungs of WT mice, which is reduced in GKO mice. These results suggest that IFN-gamma mediates the recruitment of CXCR3(+)/CD4(+) T cells into the lung via production of the chemokines IP-10, Mig, and I-TAC, resulting in granuloma formation.