Recurring environmental exposures and microbial infections have been shown to propagate a ‘Trained Immunity’ that results in a memory-based host-beneficial heterologous immune response among innate immune cells. However, the contribution of airway epithelial cells (AECs) in this trained immunity is not known. We have recently identified a large number of coding and noncoding transcripts (RNAs) that play critical role in cellular functions and a Trained Airway Immunity. Specifically, we identified novel lncRNAs and miRNAs that potentiate a hyperreactive airway response to inhalational toxicants and respiratory infections. Mechanistic studies validated the functional and molecular characteristics of these immunomodulatory RNAs. The study findings could be exploited to develop novel RNA therapeutics to help manage the debilitating lung pathologies such as allergic asthma and COPD. Moreover, the opportunistic viral infections also targeted these airway epithelial noncoding RNAs to disrupt the innate immune responses as observed in COVID-19 and HIV-associated respiratory comorbidities.Hiten Chand, Ph.D.