Journal
CLINICAL IMMUNOLOGY
Volume 230, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2021.108813
Keywords
Emphysema; Lung fibrosis; Smoking; Rheumatoid arthritis; HLA transgenic mice
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Funding
- Hurvis Foundation, Regenerative Medicine Minnesota
- Bristol Myers Squibb
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Smoking has been linked to the pathogenesis of seropositive rheumatoid arthritis (RA) and RA-associated lung disease. In arthritis-susceptible mice exposed to cigarette smoke and bleomycin, a combined pattern of fibrosis and emphysema was observed. This humanized mouse model can be a valuable research tool for understanding RA associated lung disease.
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.
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