Innate lymphoid cells in isocyanate-induced asthma: role of microRNA-155.

Autor:	Blomme EE; Dept of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium., Provoost S; Dept of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium., Bazzan E; Dept of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy., Van Eeckhoutte HP; Dept of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium., Roffel MP; Dept of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.; University of Groningen, University Medical Center Groningen, GRIAC (Groningen Research Institute for Asthma and COPD), Groningen, The Netherlands., Pollaris L; Centre for Environment and Health, KU Leuven, Leuven, Belgium., Bontinck A; Dept of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium., Bonato M; Dept of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy., Vandenbroucke L; Dept of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium., Verhamme F; Dept of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium., Joos GF; Dept of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium., Cosio MG; Dept of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.; Meakins Christie Laboratories, Respiratory Division, McGill University, Montreal, QC, Canada., Vanoirbeek JAJ; Centre for Environment and Health, KU Leuven, Leuven, Belgium., Brusselle GG; Dept of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium., Saetta M; Dept of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy., Maes T; Dept of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium tania.maes@UGent.be.
Jazyk:	angličtina
Zdroj:	The European respiratory journal [Eur Respir J] 2020 Sep 24; Vol. 56 (3). Date of Electronic Publication: 2020 Sep 24 (Print Publication: 2020).
DOI:	10.1183/13993003.01289-2019
Abstrakt:	Background: Occupational asthma, induced by workplace exposures to low molecular weight agents such as toluene 2,4-diisocyanate (TDI), causes a significant burden to patients and society. Little is known about innate lymphoid cells (ILCs) in TDI-induced asthma. A critical regulator of ILC function is microRNA-155, a microRNA associated with asthma. Objective: To determine whether TDI exposure modifies the number of ILCs in the lung and whether microRNA-155 contributes to TDI-induced airway inflammation and hyperresponsiveness. Methods: C57BL/6 wild-type and microRNA-155 knockout mice were sensitised and challenged with TDI or vehicle. Intracellular cytokine expression in ILCs and T-cells was evaluated in bronchoalveolar lavage (BAL) fluid using flow cytometry. Peribronchial eosinophilia and goblet cells were evaluated on lung tissue, and airway hyperresponsiveness was measured using the forced oscillation technique. Putative type 2 ILCs (ILC2) were identified in bronchial biopsies of subjects with TDI-induced occupational asthma using immunohistochemistry. Human bronchial epithelial cells were exposed to TDI or vehicle. Results: TDI-exposed mice had higher numbers of airway goblet cells, BAL eosinophils, CD4 + T-cells and ILCs, with a predominant type 2 response, and tended to have airway hyperresponsiveness. In TDI-exposed microRNA-155 knockout mice, inflammation and airway hyperresponsiveness were attenuated. TDI exposure induced IL-33 expression in human bronchial epithelial cells and in murine lungs, which was microRNA-155 dependent in mice. GATA3 + CD3 - cells, presumably ILC2, were present in bronchial biopsies. Conclusion: TDI exposure is associated with increased numbers of ILCs. The proinflammatory microRNA-155 is crucial in a murine model of TDI asthma, suggesting its involvement in the pathogenesis of occupational asthma due to low molecular weight agents. Competing Interests: Conflict of interest: E.E. Blomme reports grants from Fund for Scientific Research in Flanders (projects G053516N and G0G2318N) and Ghent University (BOF19-GOA-008), during the conduct of the study. Conflict of interest: S. Provoost has nothing to disclose. Conflict of interest: E. Bazzan has nothing to disclose. Conflict of interest: H.P. Van Eeckhoutte has nothing to disclose. Conflict of interest: M.P. Roffel has nothing to disclose. Conflict of interest: L. Pollaris has nothing to disclose. Conflict of interest: A. Bontinck has nothing to disclose. Conflict of interest: M. Bonato has nothing to disclose. Conflict of interest: L. Vandenbroucke has nothing to disclose. Conflict of interest: F. Verhamme has nothing to disclose. Conflict of interest: G.F. Joos reports grants and personal fees from AstraZeneca and GlaxoSmithKline, personal fees from Bayer, Eureca and Teva, grants from Chiesi, outside the submitted work; all payments were made to his employer. Conflict of interest: M.G. Cosio has nothing to disclose. Conflict of interest: J.A.J. Vanoirbeek has nothing to disclose. Conflict of interest: G.G. Brusselle has nothing to disclose. Conflict of interest: M. Saetta reports grants from Laboratori Guidotti SpA and Chiesi Farmaceutici SpA, outside the submitted work. Conflict of interest: T. Maes reports grants from Ghent University (concerted research action BOF-GOA-008) and Fund for Scientific Research in Flanders (projects G053516N and G0G2318N), during the conduct of the study; personal fees for advisory board work from GlaxoSmithKline, outside the submitted work; and is shareholder of Oryzon Genomics and Mendelion Lifesciences SL. (Copyright ©ERS 2020.)
Databáze:	MEDLINE
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