Tuesday, May 20, 2025
5/20/2025
Effects of tobacco smoking on prognosis and immune function in multiple sclerosis - PROJECT SUMMARY Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by central nervous system (CNS) inflammation and neuronal demyelination. Despite therapeutic advancements, the clinical heterogeneity among MS patients presents challenges in accurately predicting and monitoring disease progression. While previous studies have linked poor prognosis in MS patients to elevated TH17 and B cell activities, the underlying reasons for the activation of these pathways remain unclear. In our exploratory proteomic study focused on relapsing-remitting MS (RRMS) patients, we discovered that correlation between poor prognosis and heightened TH17 and B cell activation pathways is influenced by tobacco smoking. Building on our preliminary data and existing research, our central hypothesis suggests that cigarette smoke directly induces the release of damage-associated molecular patterns (DAMPs), leading to increased inflammatory TH17 and B cell activities, thereby exacerbating MS prognosis. We further propose that tobacco smoke, through exosome release of DAMPs, amplifies the inflammatory function of B cells and TH17 cells. Notably, our preliminary data indicate that B cell depletion therapy mitigates the adverse effects of smoking. This proposal has three specific aims. In Aim 1, we plan to confirm our hypothesis that tobacco smoking elevates TH17 and B cell activity by assessing immune populations in the blood of smokers and non-smokers using flow cytometry and single-cell transcriptomics. Aim 2 focuses on determining the immunological effects of B cell depletion and non-B cell depletion therapy on patients who are smokers and non-smokers. In Aim 3, we plan to identify molecular differences in exosomes from smokers and non-smokers and investigate whether smoker exosomes enhance the inflammatory function of TH17 cells and B cells. Successful completion of this project holds the potential to address critical knowledge gaps in MS research. First, it aims to provide mechanistic insights into the link between smoking, MS development, and worsened prognosis. Second, by identifying potential biomarkers in conjunction with environmental factors, this research could contribute to improved clinical management and prognosis prediction in MS.
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