In COPD, immune cells (B-cells and T-cells) form newly organized structures in the lung, follicles, which are known to play an important role in the disease progression. The formation of these structures requires the activation of a specific cellular receptor: the lymphotoxin beta receptor which is also a regulator of cell death. The death of epithelial lung cells is another feature of COPD observed in patients, preventing them from breathing effectively. We found that the blocking of lymphotoxin beta receptor signaling leads to the activation of so-called Wnt signaling. Wnt signaling is an essential pathway for lung development. In COPD patients this pathway gets switched off preventing the lung from being able to repair and regenerate.
Our work published in Nature journal offers great potential for implementing lung regenerative medicine approaches in the clinic. To achieve this ultimate goal we are testing the novel dual therapeutic approach in human clinical trials over the coming years. (See "Clinical Trials")