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

Like Comment
Occupational asthma, induced by workplace exposures to low molecular weight (LMW) agents such as toluene 2,4-diisocyanate (TDI), causes a significant burden to patients and society. Little is known about innate lymphoid cells (ILC) in TDI-induced asthma. A critical regulator of ILC function is microRNA-155, a microRNA associated with asthma.Determine whether TDI exposure modifies the number of ILC 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 ILC and T cells was evaluated in bronchoalveolar lavage fluid (BAL) by flow cytometry. Peribronchial eosinophilia and goblet cells were evaluated on lung tissue and airway hyperresponsiveness was measured with the forced oscillation technique. Putative ILC2 cells 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+ T cells and ILC, with a predominant type 2 response and tended to have airway hyperresponsiveness. In TDI-exposed microRNA-155 knockout mice, inflammation and airway hyperresponsiveness was 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.TDI exposure is associated with increased numbers of ILC. The proinflammatory microRNA-155 is crucial in a murine model of TDI asthma, suggesting its involvement in the pathogenesis of occupational asthma due to LMW agents.

Click here to read the full article @ The European respiratory journal


The wider, wiser view for healthcare professionals. ClinOwl signposts the latest clinical content from over 100 leading medical journals.
4408 Contributions
0 Following

No comments yet.