Lung Functioning and Inflammation in a Mouse Model of Systemic Juvenile Idiopathic Arthritis

Bert Malengier-Devlies, Tatjana Decaesteker, Kaat Dekoster, Arno Vanstapel, Kourosh Ahmadzadeh, Fariba Poosti, Tania Mitera, Laura Seldeslachts, Erik Verbeken, Carine Wouters, Greetje Vande Velde, Jeroen Vanoirbeek, Patrick Matthys

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Systemic juvenile idiopathic arthritis (sJIA) is an immune disorder characterized by fever, skin rash, arthritis and splenomegaly. Recently, increasing number of sJIA patients were reported having lung disease. Here, we explored lung abnormalities in a mouse model for sJIA relying on injection of IFN-γ deficient (IFN-γ KO) mice with complete Freund's adjuvant (CFA). Monitoring of lung changes during development of sJIA using microcomputer tomography revealed a moderate enlargement of lungs, a decrease in aerated and increase in non-aerated lung density. When lung function and airway reactivity to methacholine was assessed, gender differences were seen. While male mice showed an increased tissue hysteresivity, female animals were characterized by an increased airway hyperactivity, mirroring ongoing inflammation. Histologically, lungs of sJIA-like mice showed subpleural and parenchymal cellular infiltrates and formation of small granulomas. Flow cytometric analysis identified immature and mature neutrophils, and activated macrophages as major cell infiltrates. Lung inflammation in sJIA-like mice was accompanied by augmented expression of IL-1β and IL-6, two target cytokines in the treatment of sJIA. The increased expression of granulocyte colony stimulating factor, a potent inducer of granulopoiesis, in lungs of mice was striking considering the observed neutrophilia in patients. We conclude that development of sJIA in a mouse model is associated with lung inflammation which is distinct to the lung manifestations seen in sJIA patients. Our observations however underscore the importance of monitoring lung disease during systemic inflammation and the model provides a tool to explore the underlying mechanism of lung pathology in an autoinflammatory disease context.

Original languageEnglish
Pages (from-to)642778
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - 2021

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Arthritis, Juvenile/complications
  • Disease Models, Animal
  • Female
  • Freund's Adjuvant/immunology
  • Inflammation/etiology
  • Inflammation Mediators/analysis
  • Interferon-gamma/physiology
  • Lung/immunology
  • Macrophage Activation
  • Male
  • Mice
  • Mice, Inbred BALB C

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