Defining the Immune States of the Cholinergic Anti-Inflammatory Pathway in Obesity-Driven Chronic Inflammation 4692

Abstract Description Background Obesity is a state of chronic low-grade inflammation, where alterations in the immune landscape plays a central role. Cholinergic anti-inflammatory pathway (CAP), mediated by acetylcholine (ACh) and its receptor α7nAChR, is an effective counter regulatory mechanisms to suppress pro-inflammatory cytokines. Methods Immune profiling of PBMCs from obese and non-obese individuals was performed using mass cytometry. Unpaired t test identified significant differences in CAP among immune cells. Results Our data reveal significantly elevated levels of α7nAChR+ monocytes and B cells, along with increased ACh-expressing CD8+/CD4+ T cells, and Tregs including monocytes and B cells in obese vs. non-obese individuals. For the first time, we define CAP heterogeneity, showing ACh dominance in activated Teff and Treg cells, while nAChRs are primarily expressed on classical and non-classical monocytes. Key metabolic markers: C-reactive protein, dyslipidemia, and HbA1c, were positively correlated with ACh-expressing T cells, α7nAChR+ monocytes, and B cells, Discussion: This study is the first to report elevated levels of ACh and its receptors across immune cells in human. Future studies should investigate CAP’s functional role and interaction with Tregs highlighting its therapeutic potential. Conclusion This increase in CAP components may reflect an adaptive response to chronic inflammation or a dysfunction where heightened CAP activity fails to regulate inflammation effectively. Funding Sources University of Minneosta Medical School Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)