title: IL-12 overexpression in mice as a model for Sjögren lung disease.
abstract: Interleukin-12 (IL-12), a Th1 proinflammatory cytokine, is reported to be increased in Sjögren syndrome. To evaluate the effects of local Th1/Th2 deregulation, we generated a transgenic mouse model that overexpresses IL-12 in the lungs. IL-12 transgenic mice developed bronchial and alveolar abnormalities strikingly similar to those found in the lungs of Sjögren patients. Pathologically, lung abnormalities began at approximately 4 mo of age and were characterized by lymphocytic infiltrates around the bronchi, intraluminal periodic acid Schiff-positive debris, increased cell proliferation in the alveolar region, and increased interstitial and alveolar macrophages. Functionally, these abnormalities translated into decreased mucociliary clearance (P<0.05 vs. wild-type littermates) and increased oxidative stress (P<0.01). The pathological and functional abnormalities were accompanied by significant changes in lung natural killer (NK) cells. The number of NK cells was fourfold higher in IL-12 transgenic than wild-type lungs (20% of all lymphoid cells vs. 5%) during the first month of life. NK cells then decreased within a narrow window of time (from 30 to 50 days of age), reaching a nadir of approximately 2% on day 50, and remained at these low levels thereafter. This new mouse model highlights the role of IL-12 in the initiation of Sjögren syndrome.
authors.affiliation: Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: McGrath-Morrow
authors.forename: Beth
authors.initials: B
authors.lastname: Laube
authors.forename: Shey-Cherng
authors.initials: SC
authors.lastname: Tzou
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cho
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cleary
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.forename: Noel R
authors.initials: NR
authors.lastname: Rose
authors.forename: Patrizio
authors.initials: P
authors.lastname: Caturegli
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000473:pathology; D007765:Lacrimal Apparatus / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009079:Mucociliary Clearance; D018384:Oxidative Stress; D010503:Periodic Acid-Schiff Reaction; D012469:Salivary Glands / Q000473:pathology; D015398:Signal Transduction; D012859:Sjogren's Syndrome / Q000150:complications*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D018664:Interleukin-12