Transcriptomic changes in bronchoalovelar derived macrophages after expsoure to whole body cigarette smoke exposure (8 weeks)

Chronic obstructive pulmonary disease (COPD) is an inflammatory airway disease characterized by emphysema and chronic bronchitis and a leading cause of mortality worldwide. COPD is commonly associated with several comorbid diseases which contribute to worse patient outcomes. Cigarette smoke (CS) is the most prominent risk factor for COPD development and progression and is known to be detrimental to numerous effector functions of lung resident immune cells, including phagocytosis and cytokine production. Methods: C57BL/6 mice were exposed to 8 weeks of CS as an experimental model of COPD. Airspace macrophages (AMs) were isolated from CS-exposed and RA mice and bulk RNA-Seq performed. The functional role of differentially expressed genes was assessed through gene ontology analyses. Ingenuity Pathway Analysis was used to determine the activation states of canonical pathways and upstream regulators enriched in differentially expressed genes in AMs. Results: CS induced decreased expression of genes involved in pathogen response, phagosome formation, and immune cell trafficking in AMs. Conclusions: CS exposure can induce transcriptomic remodelling in AMs. Our study highlights the ability of CS exposure to affect immune cell populations distal to the lung and warrants further investigation into the functional effects of these changes and the ensuing role in driving multimorbid disease. Overall design: C57BL/6J wild type mice (Stock No. 000664) were purchased from The Jackson Laboratory and were maintained under specific pathogen-free conditions at Weill Cornell Medicine. Sex and age-matched mice aged between 6-12 weeks of age were exposed to whole-body CS using the Teague Enterprises TE-10 inhalation exposure apparatus and 3R4F cigarettes acquired from the University of Kentucky Centre for Reference Products. Mice were exposed to CS (average total particulate matter (TPM) of 150 mg/m3) for a minimum of 2 hours per day for 5 days a week, for an 8-week period.