The role of lipocalin-2 in lung homeostasis, inflammation response, and recovery following organic dust exposure

Agricultural industry workers are frequently exposed to harmful dust particles and consequently have a higher risk of developing chronic lung inflammatory conditions such as chronic obstructive pulmonary disease (COPD). Lipocalin-2 (LCN-2) is an innate immune protein with paradoxical roles in both pro- and anti-inflammatory responses at mucosal sites; however, its role in the lung during homeostatic and inflammatory states, such as those induced by inhaled dusts, remain unknown. Here, we investigated the role of LCN-2 in a murine model of organic dust exposure-induced lung inflammation using wildtype C57Bl/6 (WT) and LCN-2 knockout (KO) mice exposed repetitively to extracts of dusts (DE) collected from swine confinement facilities. Repetitive DE exposure consisted of fifteen days of intranasal instillations with and without a three-day recovery period. Through these investigations, we identified an important function of LCN-2 in regulating tissue homeostasis and recovery following inflammatory injury in the lung. Additionally, compartmentalized effects on T cell and macrophage levels were observed in bronchoalveolar lavage fluid (BALF) vs. lung tissue in DE-exposed LCN-2 KO mice versus WT mice. Ablation of LCN-2 resulted in deficits in resolving histopathological markers of inflammation, and decreased levels of IL-10 after DE. Exogenous IL-10 administration partially rescued indicators of inflammation in LCN-2 KO mice after DE exposure. Taken together, these investigations highlight a novel role for LCN-2 in regulating lung homeostasis, inflammation response, and repair following organic dust-induced inflammation that may be mediated, at least in part, by IL-10.