title: A novel model of rheumatoid arthritis-associated interstitial lung disease in SKG mice.
abstract: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is associated with increased mortality in up to 10% of patients with rheumatoid arthritis. Lung exposure to cigarette smoke has been implicated in disease development. Little is known about the mechanisms underlying the development of RA-ILD, in part due to the lack of an appropriate mouse model. The objectives of this study were (i) to test the suitability of SKG mice as a model of cellular and fibrotic interstitial pneumonia in the setting of autoimmune arthritis, and (ii) to determine the role of lung injury in the development of arthritis in SKG mice. Lung tissues were evaluated in arthritic SKG mice by quantifying cell accumulation in bronchoalveolar lavage, static compliance, collagen levels, and infiltrating cell phenotypes by flow cytometry and histology. Lung injury was induced by exposure to cigarette smoke or bleomycin. Arthritic SKG mice developed a patchy cellular and fibrotic interstitial pneumonia associated with reduced static compliance, increased collagen levels, and accumulation of inflammatory cells. Infiltrating cells comprised CD4+ T cells, B cells, macrophages, and neutrophils. Chronic exposure to cigarette smoke or initiation of lung injury with bleomycin did not cause arthritis. The pattern of lung disease suggests that arthritic SKG mice represent an authentic model of nonspecific interstitial pneumonia in RA-ILD patients. The lack of arthritis development after cigarette smoke or lung injury suggests that a model where breaches in immunologic tolerance are induced by lung inflammation and injury alone may be overly simplistic.
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Keith
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Powers
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Redente
authors.forename: Amen
authors.initials: A
authors.lastname: Sergew
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Alison
authors.initials: A
authors.lastname: Gizinski
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: David W H
authors.initials: DW
authors.lastname: Riches
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D001761:Bleomycin / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008170:Lung Compliance / Q000187:drug effects; D017563:Lung Diseases, Interstitial / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D012906:Smoke / Q000009:adverse effects
chemical_list: D012906:Smoke; D001761:Bleomycin; D003094:Collagen