Innate lymphoid cells in isocyanate-induced asthma: role of microRNA-155.
Journal
The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
28
06
2019
accepted:
10
05
2020
pubmed:
6
6
2020
medline:
22
6
2021
entrez:
6
6
2020
Statut:
epublish
Résumé
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. 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. 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. TDI-exposed mice had higher numbers of airway goblet cells, BAL eosinophils, CD4 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.
Sections du résumé
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
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.
Identifiants
pubmed: 32499335
pii: 13993003.01289-2019
doi: 10.1183/13993003.01289-2019
pii:
doi:
Substances chimiques
MIRN155 microRNA, human
0
MicroRNAs
0
Mirn155 microRNA, mouse
0
Toluene 2,4-Diisocyanate
17X7AFZ1GH
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright ©ERS 2020.
Déclaration de conflit d'intérêts
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.