The role of the vitamin D pathway in airway innate immunity of chronic obstructive pulmonary disease.

This project aims to unravel the role of vitD signaling in the innate immunity of COPD, particularly NF- B driven inflammation and macrophage function. More specifically, we will assess in a smoking mouse model whether vitD signaling is impaired in smoke-exposed lungs, whether smoke-induced changes in vitD signaling correlate with COPD progression, NF- B inflammation and macrophage dysfunction, and whether vitD receptor ablation and/or severe vitD deficiency enhances these processes. Observations in mice will be further explored on human material. Expression profiles of key elements in vitD and NF- B pathway, and their relationship with potential regulators such as histone deacetylases, will be measured on lung specimens of COPD subjects and controls. Primary cell cultures will be used to address the potential of vitD (-analogues) with or without HDAC activators, in reducing inflammation and improving bacterial clearance. Together, obtained insights may result in new intervention studies targeting particular subgroups of COPD.