Non-redundant functions of IL-6 produced by macrophages and dendritic cells in allergic airway inflammation
Gubernatorova, Ekaterina O. (Russian Academy of Sciences. Engelhardt Institute of Molecular Biology)
Gorshkova, Ekaterina A. (Russian Academy of Sciences. Engelhardt Institute of Molecular Biology)
Namakanova, Olga A. (Russian Academy of Sciences. Engelhardt Institute of Molecular Biology)
Zvartsev, Ruslan (Russian Academy of Sciences. Engelhardt Institute of Molecular Biology)
Hidalgo Pareja, Juan (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Drutskaya, Marina S. (Lomonosov Moscow State University)
Tumanov, Alexei V. (University of Texas Health Science Center at San Antonio. Department of Microbiology, Immunology and Molecular Genetics)
Nedospasov, Sergei A. (Lomonosov Moscow State University)

Date:	2018
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.
Grants:	Ministerio de Economía y Competitividad SAF2014-56546-R
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	HDM-induced asthma ; Eosinophils ; Neutrophils ; Mouse models ; House dust mite (HDM)
Published in:	Frontiers in immunology, Vol. 9 (November 2018) , art. 2718, ISSN 1664-3224

DOI: 10.3389/fimmu.2018.02718
PMID: 30534125

2.5 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles