@article{10.1172/jci.insight.87168, author = {Kong Chen AND Brian T. Campfield AND Sally E. Wenzel AND Jeremy P. McAleer AND James L. Kreindler AND Geoffrey Kurland AND Radha Gopal AND Ting Wang AND Wei Chen AND Taylor Eddens AND Kathleen M. Quinn AND Mike M. Myerburg AND William T. Horne AND Jose M. Lora AND Brian K. Albrecht AND Joseph M. Pilewski AND Jay K. Kolls}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Antiinflammatory effects of bromodomain and extraterminal domain inhibition in cystic fibrosis lung inflammation}, year = {2016}, month = {7}, volume = {1}, url = {https://insight.jci.org/articles/view/87168}, abstract = {Significant morbidity in cystic fibrosis (CF) results from chronic lung inflammation, most commonly due to Pseudomonas aeruginosa infection. Recent data suggest that IL-17 contributes to pathological inflammation in the setting of abnormal mucosal immunity, and type 17 immunity–driven inflammatory responses may represent a target to block aberrant inflammation in CF. Indeed, transcriptomic analysis of the airway epithelium from CF patients undergoing clinical bronchoscopy revealed upregulation of IL-17 downstream signature genes, implicating a substantial contribution of IL-17–mediated immunity in CF lungs. Bromodomain and extraterminal domain (BET) chromatin modulators can regulate T cell responses, specifically Th17-mediated inflammation, by mechanisms that include bromodomain-dependent inhibition of acetylated histones at the IL17 locus. Here, we show that, in vitro, BET inhibition potently suppressed Th17 cell responses in explanted CF tissue and inhibited IL-17–driven chemokine production in human bronchial epithelial cells. In an acute P. aeruginosa lung infection murine model, BET inhibition decreased inflammation, without exacerbating infection, suggesting that BET inhibition may be a potential therapeutic target in patients with CF.}, number = {11}, doi = {10.1172/jci.insight.87168}, url = {https://doi.org/10.1172/jci.insight.87168}, }