Increased Hematopoietic Extracellular RNAs and Vesicles in the Lung during Allergic Airway Responses

Extracellular RNAs (exRNAs) can be released by numerous cell types in vitro, are often protected within vesicles, and can modify recipient cell function. To determine how the composition and cellular sources of exRNAs and the extracellular vesicles (EVs) that carry them change in vivo during tissue inflammation, we analyzed bronchoalveolar lavage fluid (BALF) from mice before and after lung allergen challenge. In the lung, extracellular microRNAs (ex-miRNAs) had a composition highly correlated with airway lining epithelium. Using cell-type specific membrane tagging and single vesicle flow, we also found that 80% of detected vesicles were of epithelial origin. After the induction of allergic airway inflammation, miRNAs selectively expressed by immune cells, including miR-223 and miR-142a, increased and hematopoietic cell derived EVs also increased >2-fold. Together these data demonstrate that infiltrating immune cells release ex-miRNAs and EVs in inflamed tissues to alter the local extracellular environment. Expression analysis of extracellular miRNAs from biofluids (airway lining fluid and serum) and miRNAs from cells in the lung (airway immune cells and pulmonary epithelium) during airway allergic responses in a mouse model of asthma.