MicroRNAs are epigenetic regulatory factors capable of silencing the expression of target genes and might mediate the effects of air pollution on health. The objective of the present population-based study was to investigate the association between microRNA expression and long-term, residential exposure to atmospheric PM₁₀ and NO₂. We included 998 non-smoking adult participants from the cross-sectional ELISABET survey (2010-2014) in the Lille urban area of France. The mean residential annual pollution levels were estimated with an atmospheric dispersion modelling system. Ten microRNAs were selected on the basis of the literature data, together with two housekeeping microRNAs (miR-93-5p and miR-191-5p) and were quantified with RT-qPCRs. Multivariate linear regression models were used to study the association between microRNAs and air pollution. The threshold for statistical significance (after correction for the FDR) was set to p < 0.1. The mean annual exposure between 2011 and the year of inclusion was 26.4 ± 2.0 µg/m³ for PM₁₀ and 24.7 ± 5.1 µg/m³ for NO₂. Each 2 µg/m³ increment in PM₁₀ exposure was associated with an 8.6% increment (95%CI [3.1; 14.3]; p_FDR = 0.019) in miR-451a expression. A 5 µg/m³ increment in NO₂ exposure was associated with a 5.3% increment ([0.7; 10]; p_FDR = 0.056) in miR451a expression, a 3.6% decrement (95%CI [-6.1; -1.1]; p_FDR = 0.052) in miR-223-3p expression, a 3.8% decrement (95%CI[-6.8; -0.7]; p_FDR = 0.079) in miR-28-3p expression, a 4.3% decrement (95%CI [-7.7; -0.8]; p_FDR = 0.055) in miR-146a-5p expression, and a 4.0% decrement (95% CI[-7.4; -0.4]; p_FDR = 0.059) in miR-23a-5p expression. The difference between the two housekeeping microRNAs miR-93-5p and miR-191-5p was also associated with PM₁₀ and NO₂ exposure. Our results suggest that circulating miRNAs are potentially valuable biomarkers of the effects of air pollution.

Although the effects of cigarette smoke (CS) on the development of several intestinal diseases is well documented, the impact of e-cigarette aerosol (e-cig) on digestive health is largely unknown. To compare the effects of e-cig and CS on mouse ileum and colon, animals were chronically exposed for 6 months by nose-only inhalation to e-cig at 18 or 30 W power, or to 3R4F CS. Results showed that e-cig exposure decreased colon cell proliferation. Several other proliferative defects were observed in response to both e-cig and CS exposure, including up- and down-regulation of cyclin D1 protein levels in the ileum and colon, respectively. E-cig and CS exposure reduced myeloperoxidase activity in the ileum. In the colon, both exposures disrupted gene expression of cytokines and T cell transcription factors. For tight junction genes, ZO-1- and occludin-protein expression levels were reduced in the ileum and colon, respectively, by e-cig and CS exposure. The 16S sequencing of microbiota showed specific mild dysbiosis, according to the type of exposure. Overall, e-cig exposure led to altered proliferation, inflammation, and barrier function in both the ileum and colon, and therefore may be a gut hazard on par with conventional CS.

Introduction: Although the direct contribution of air pollution to the onset and exacerbations of asthma is well established, the consequences of maternal exposure on offspring remain insufficiently understood. Ultrafine particles (UFPs) are of particular concern because of their ability to escape phagocytosis by alveolar macrophages, cross the alveolo-capillary barrier (ACB), and reach the systemic circulation. Even without direct mixing of maternal and fetal blood, placental exchanges may allow pollutants or associated signals to influence fetal development. The ASMAPUF project aims to decipher the immunological and epigenetic mechanisms linking gestational exposure to UFPs with asthma risk in the offspring. Methods: Pregnant C57BL/6 mice are intranasally exposed to UFPs throughout gestation. Offspring are subsequently sensitized and challenged with the house dust mite allergen to trigger allergic airway inflammation. After sacrifice, immune and epigenetic alterations are investigated in several tissues, including lungs, brain, and blood. Complementary in vitro experiments use a co-culture of epithelial and endothelial cells maintained at an air–liquid interface to evaluate ACB permeability and mechanisms promoting the systemic passage of UFPs. Particular attention is paid to IL-33, a key alarmin in asthma pathophysiology. We hypothesize that maternal exposure to UFPs enhances IL-33 production in placental and/or fetal tissues, contributing to inflammatory imprinting and epigenetic regulation in the progeny. Conclusion: By combining murine models and mechanistic in vitro approaches, this ongoing project seeks to identify how prenatal exposure to UFPs programs immune responses and promotes the later development of allergic asthma.