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pubmed:abstractText |
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 (SR). 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.
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