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

EO Gubernatorova, EA Gorshkova, OA Namakanova, RV Zvartsev, J Hidalgo, MS Drutskaya, AV Tumanov, A. Sergei, SA. Nedospasov

Research output: Contribution to journalArticleResearch

9 Citations (Scopus)

Abstract

© 2007 - 2018 Frontiers Media S.A. 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
Article number02718
Pages (from-to)2718-
JournalFrontiers in Immunology
Volume9
DOIs
Publication statusPublished - 26 Nov 2018

Keywords

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

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