Lower respiratory infections, caused by pathogens such as Influenza A Virus (IAV), are a leading cause of mortality and morbidity. The main therapeutic strategies against IAV focused on reducing viral burden have been unsuccessful, urging the need for novel therapeutic strategies to strengthen host immune response. The circadian clock controls several aspects of host-pathogen interaction, making it a valuable research topic regarding lung immunology. Previous work in the Sengupta lab has shown that circadian rhythms provide a time-of-day specific protection from mortality in IAV that is lost in clock-disrupted mice. 

This projects aims to determine how environmental lighting may affect lung repair and regeneration, specifically looking at ATII cells. ATII progenitor cells, responsible for restoring lost epithelial cells and regenerating ATI cells, are critical in lung repair and regeneration. Using fluorescent immunohistochemistry and manual counting methods, the percentage of Sftpc+ (ATII marker) cells was calculated to assess the regenerative capacity of each lung sample. Our results show a significantly lower Sftpc+ cell percentage in the LL and Dusk groups relative to the Dawn group, indicating fewer ATII cells and that the disruption of light cycling following influenza infection adversely impacts lung repair and regeneration. Further investigation into whether the lower ATII cell count is due to more cell death or less proliferation will be useful. These results help elucidate certain aspects of circadian gating of lung injury and have clinical implications including but not limited to targeting circadian gene products and timing drugs and vaccinations to the host circadian clock.