Non-redundant functions of IL-6 produced by macrophages and dendritic cells in allergic airway inflammation

Ekaterina O. Gubernatorova, Ekaterina A. Gorshkova, Olga A. Namakanova, Ruslan V. Zvartsev, Juan Hidalgo, Marina S. Drutskaya, Alexei V. Tumanov, Sergei A. Nedospasov

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7 Scopus citations

Abstract

Asthma is a common inflammatory disease of the airway caused by a combination of genetic and environmental factors and characterized by airflow obstruction, wheezing, eosinophilia, and neutrophilia of lungs and sputum. Similar to other proinflammatory cytokines, IL-6 is elevated in asthma and plays an active role in this disease. However, the exact molecular mechanism of IL-6 involvement in the pathogenesis of asthma remains largely unknown and the major cellular source of pathogenic IL-6 has not been defined. In the present study, we used conditional gene targeting to demonstrate that macrophages and dendritic cells are the critical sources of pathogenic IL-6 in acute HDM-induced asthma in mice. Complete genetic inactivation of IL-6 ameliorated the disease with significant decrease in eosinophilia in the lungs. Specific ablation of IL-6 in macrophages reduced key indicators of type 2 allergic inflammation, including eosinophil and Th2 cell accumulation in the lungs, production of IgE and expression of asthma-associated inflammatory mediators. In contrast, mice with deficiency of IL-6 in dendritic cells demonstrated attenuated neutrophilic, but regular eosinophilic response in HDM-induced asthma. Taken together, our results indicate that IL-6 plays a pathogenic role in the HDM-induced asthma model and that lung macrophages and dendritic cells are the predominant sources of pathogenic IL-6 but contribute differently to the disease.

Original languageEnglish (US)
Article number2718
JournalFrontiers in immunology
Volume9
Issue numberNOV
DOIs
StatePublished - Nov 26 2018

Keywords

  • HDM-induced asthma
  • eosinophils
  • house dust mite (HDM)
  • mouse models
  • neutrophils

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Gubernatorova, E. O., Gorshkova, E. A., Namakanova, O. A., Zvartsev, R. V., Hidalgo, J., Drutskaya, M. S., Tumanov, A. V., & Nedospasov, S. A. (2018). Non-redundant functions of IL-6 produced by macrophages and dendritic cells in allergic airway inflammation. Frontiers in immunology, 9(NOV), [2718]. https://doi.org/10.3389/fimmu.2018.02718