IL-12 overexpression in mice as a model for Sjögren lung disease

Sharon A McGrath-Morrow, Beth L Laube, Shey Cherng Tzou, Cecilia Cho, Jeffrey Cleary, Hiroaki Kimura, Noel R. Rose, Patrizio P Caturegli

Research output: Contribution to journalArticle

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 ∼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 ∼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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume291
Issue number4
DOIs
StatePublished - 2006

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Interleukin-12
Lung Diseases
Lung
Natural Killer Cells
Transgenic Mice
Mucociliary Clearance
Periodic Acid
Alveolar Macrophages
Bronchi
Oxidative Stress
Cell Proliferation
Lymphocytes
Cytokines

Keywords

  • Autoimmunity
  • Inflammation
  • Natural killer cells
  • Transgenic mice

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

IL-12 overexpression in mice as a model for Sjögren lung disease. / McGrath-Morrow, Sharon A; Laube, Beth L; Tzou, Shey Cherng; Cho, Cecilia; Cleary, Jeffrey; Kimura, Hiroaki; Rose, Noel R.; Caturegli, Patrizio P.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 291, No. 4, 2006.

Research output: Contribution to journalArticle

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