IL-33 signalling contributes to pollutant-induced allergic airway inflammation

Background: Clinical and experimental studies have identified a crucial role for IL-33 and its receptor ST2 in allergic asthma. Inhalation of traffic-related pollutants, such as diesel exhaust particles (DEP), facilitates the development of asthma and can cause exacerbations of asthma. However, it is unknown whether IL-33/ST2 signalling contributes to the enhancing effects of air pollutants on allergic airway responses. Objective: We aim to investigate the functional role of IL-33/ST2 signalling in DEP-enhanced allergic airway responses, using an established murine model. Methods: C57BL/6J mice were exposed to saline, DEP alone, house dust mite (HDM) alone or combined DEP+HDM. To inhibit IL-33 signalling, recombinant soluble ST2 (r-sST2) was given prophylactically (ie, during the whole experimental protocol) or therapeutically (ie, at the end of the experimental protocol). Airway hyperresponsiveness and the airway inflammatory responses were assessed in bronchoalveolar lavage fluid (BALF) and lung. Results: Combined exposure to DEP+HDM increased IL-33 and ST2 expression in lung, elevated inflammatory responses and bronchial hyperresponsiveness compared to saline, sole DEP or sole HDM exposure. Prophylactic interference with the IL-33/ST2 signalling pathway impaired the DEP-enhanced allergic airway inflammation in the BALF, whereas effects on lung inflammation and airway hyperresponsiveness were minimal. Treatment with r-sST2 at the end of the experimental protocol did not modulate the DEP-enhanced allergic airway responses. Conclusion: Our data suggest that the IL-33/ST2 pathway contributes to the onset of DEP-enhanced allergic airway inflammation

The role of miR-155 in cigarette smoke-induced pulmonary inflammation and COPD

Chronic obstructive pulmonary disease (COPD) is a highly prevalent respiratory disease characterized by airflow limitation and chronic inflammation. MiR-155 is described as an ancient regulator of the immune system. Our objective was to establish a role for miR-155 in cigarette smoke (CS)-induced inflammation and COPD. We demonstrate increased miR-155 expression by RT-qPCR in lung tissue of smokers without airflow limitation and patients with COPD compared to never smokers and in lung tissue and alveolar macrophages of CS-exposed mice compared to air-exposed mice. In addition, we exposed wild type and miR-155 deficient mice to CS and show an attenuated inflammatory profile in the latter. Alveolar macrophages were sorted by FACS from the different experimental groups and their gene expression profile was analyzed by RNA sequencing. This analysis revealed increased expression of miR-155 targets and an attenuation of the CS-induced increase in inflammation-related genes in miR-155 deficient mice. Moreover, intranasal instillation of a specific miR-155 inhibitor attenuated the CS-induced pulmonary inflammation in mice. Finally, elastase-induced emphysema and lung functional changes were significantly attenuated in miR-155 deficient mice. In conclusion, we highlight a role for miR-155 in CS-induced inflammation and the pathogenesis of COPD, implicating miR-155 as a new therapeutic target in COPD

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

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