| Popis: |
Background: Whereas occupational asthma, induced by workplace exposures to allergens or respiratory sensitizers, such as toluene 2,4-diisocyanate (TDI), causes a significant burden to patients and society, its pathogenesis still needs to be fully elucidated. Although the adaptive responses have been characterized previously, there is little information about the role of innate lymphoid cells (ILC) in TDI-induced asthma. A critical regulator of ILC function is microRNA-155 (miR-155), a miR associated with asthma pathogenesis. In a mouse model we investigated changes in ILC subsets upon isocyanate exposure and assessed whether miR-155 contributes to TDI-induced airway inflammation and hyperresponsiveness (AHR). Methods: C57BL/6 and miR-155 knockout (KO) mice received 2%TDI or vehicle (acetone/olive oil) on each ear (day 1, 8), followed by oropharyngeal instillations of 0.01%TDI or vehicle (day 15, 22, 29). On day 31, inflammation was evaluated in bronchoalveolar lavage fluid (BALF) by flow cytometry. AHR was measured with the forced oscillation technique. Lung sections were stained with Congo Red or periodic acid-Schiff. Results: TDI-exposed mice had higher numbers of BALF cells, eosinophils, neutrophils, CD11b+ DCs, CD8+ and CD4+ T cells and ILC. All T helper and ILC populations (IFN-?+ ILC1, IL-13+ ILC2, IL-17+ ILC3) were elevated, with a predominant type 2 response. TDI-exposed mice had higher numbers of lung eosinophils and goblet cells and tended to have AHR. The inflammation and AHR was attenuated in the TDI-exposed miR-155 KO mice. Conclusion: In a model of TDI-induced asthma, the inflammation is attenuated in miR-155 KO mice, suggesting a pro-inflammatory role of this miR in the pathogenesis of occupational asthma. |
