Effects of Early Life Environmental Tobacco Smoke Exposure on Pulmonary Immunity

There is a long history detailing the health hazards of cigarette smoking and secondhand, or environmental tobacco smoke. More recently evidence has suggested that children that have reduced pulmonary function are more likely to grow into adults with reduced lung function. Severe respiratory infection and exposure to tobacco smoke are strongly associated with reduced lung function in early childhood, and exposure to environmental tobacco smoke is a contributing factor for increased number and frequency of respiratory infections. Despite declining tobacco usage in the United States, smoking globally continues to be a major public health issue, and novel inhalation exposures such as electronic cigarette usage and exposure to wildfire smoke from wildland-urban interfaces have become an increasing burden on human health. Tobacco smoke research is highly standardized and replicable, and tobacco smoke contains many classes of chemicals that may be concern from novel exposures. In this study, we examine the persistent impact of environmental tobacco smoke exposure on lung pathophysiology using a murine model of neonatal exposure. We found neonatal environmental tobacco smoke exposure resulted in sexually dimorphic responses with female but not male mice having increased lung damage and airways immune cells in adulthood, and using RNA-sequencing, we found neonatal environmental tobacco smoke exposure in female mice significantly altered Hallmark Pathways. We report a mechanism by which neonatal tobacco smoke exposure transiently induces an IL-22+ ILC3 population and that IL-22 modulates club cell secretory protein to alter lung function. Later in life, we found that neonatal environmental tobacco smoke exposure resulted in elevated macrophages in female but not male mice with novel alterations in gene expression in the lungs