Smoking Tobacco Increases Extracellular Vesicles and Alters Their Cargo in the Blood of Multiple Sclerosis Patients 2259575

Abstract

Abstract Introduction Multiple sclerosis (MS) is a chronic disease of the central nervous system that is characterized by a widely variable prognosis. While some patients experience a relatively mild course, others suffer from severe disease progression. Tobacco smoke is an environmental factor known to worsen MS outcomes; however, the mechanism by which it exerts its detrimental effects is unclear. Methods We used the OLINK-Explore assay to profile 1,466 serum proteins in MS patients who were smokers or non-smokers, as well as in healthy controls. Extracellular vesicles (EVs) were isolated, and mass spectrometry was performed to identify differentially abundant proteins. In vitro experiments using cigarette smoke extract (CSE) were conducted to assess EV release from immune cells, including T cells, B cells, and monocytes. Additionally, a 3-D human airway tissue model was utilized to identify the primary cell types producing vesicles in the lung microenvironment. Results Smoking significantly increased levels of proteins associated with the EV cellular compartment, an effect more pronounced in patients compared to healthy individuals. Isolation of EVs confirmed that MS smokers had significantly more plasma exosomes (30—150 nm vesicles) compared to non-smoker patients and healthy non-smokers. Mass spectrometry of exosomes revealed 20 differentially abundant proteins, including elevated SerpinA1 in non-smokers and Trim33 in smokers. In vitro, CSE directly induced EV release from immune cells, with monocytes identified as the major contributors in the 3-D human airway tissue model. Conclusion These findings suggest that tobacco smoke drives the release of extracellular vesicles, potentially exacerbating immune cell dysfunction in MS. Ongoing research aims to further characterize the cargo and functional differences of EVs in smoker and non-smoker patients to better understand their role in disease. Funding Source NIH, Presbyterian Health Foundation Topic Categories Basic Autoimmunity (BA)