Autoimmune induction of a COPD-like inflammatory phenotype in mice

Chronic obstructive pulmonary disease (COPD) is a highly prevalent inflammatory disease of the lung associated with increasing mortality rates throughout the world. Tobacco smoke exposure has been identified as most common cause of COPD, however, the pathogenetic mechanisms leading to disease development are still poorly understood. Most recently, autoimmune mechanisms probably directed against degraded components of the extracellular matrix came into discussion to contribute to induction and/or perpetuation of the disease-underlying inflammatory processes. Based on these observations we hypothesized that experimental induction of a Th1-driven autoimmune response to elastin may result in a COPD-like inflammatory phenotype in the lungs of mice.

To test this hypothesis, we initially immunized C57Bl/6 mice to bovine elastin (69.8% homology to mouse elastin) and applied several booster immunizations using a mixture of bovine and rat elastin (86.3% homology). We analyzed the development of mouse elastin-specific autoantibodies and characterized the induction of an inflammatory response in the lungs. To further elucidate the role of Th1 cells experiments were performed in Tbet-/- mice in parallel.

Over time, increasing titers of anti-mouse-elastin IgG antibodies were detected indicating a successful induction of an autoimmune immune response. Additionally, at day 140 of the protocol increased lymphocyte levels were observed in the bronchoalveolar lavage and in lung homogenates. Histologically, peripheral inflammatory foci comparable to those observed in lungs of COPD patients as well as peribronchial inflammation processes were observed. Both, induction of autoantibodies as well as the inflammatory response in the lungs was less pronounced in Tbet-/- mice even though not completely absent.

In future, subsequent analyses will be performed to further characterize the nature of elastin-induced autoimmune lung inflammation. Moreover, the model will be combined with continuous cigarette-smoke exposure to evaluate the role of such environmental influences on the induction/perpetuation of autoimmune inflammatory processes in the lung.