A novel humanized model of rheumatoid arthritis associated lung disease

Abstract

Cigarette smoking has been implicated in the pathogenesis of seropositive rheumatoid arthritis (RA), as well as RA-associated lung disease. Fibrotic interstitial lung disease as well as emphysema occur in RA and cause substantial morbidity. We used arthritis-susceptible HLA-DQ8 transgenic mice to generate RA-associated lung disease. Mice were exposed to cigarette smoke (CS) prior to induction of arthritis, and subsequently injected with a low dose of bleomycin intra-tracheally to induce lung injury. Exposure of arthritic mice to both CS and bleomycin led to a significant reduction in lung compliance consistent with development of diffuse lung disease. Morphologic evaluation of the lung demonstrated areas of emphysematous change and co-existent fibrosis, consistent with a combined pattern of fibrosis and emphysema. These changes were accompanied by inflammatory cell infiltration and upregulation of fibrosis-associated genes. This humanized mouse model can serve as a valuable research tool to understand the pathogenesis of RA associated lung disease.