Rapid Neurochemical Signaling from Regulatory T cells Reveals a Novel Dimension of Immune Modulation 2258988

Abstract Introduction Neurochemicals are key mediators of neuro-immune crosstalk, modulating communication between immune cells and neurons. Dysregulation of this bidirectional communication has been implicated in neuroinflammatory and neurodegenerative diseases. While immune cells possess the machinery to synthesize and respond to neurochemicals, the mechanisms and dynamics of neurochemical signaling, especially from T cells, remain poorly understood. Among T cells, regulatory T cells (Tregs) are crucial in maintaining immune homeostasis through well-established suppressive functions. However, their potential involvement in rapid neurochemical communication remains unexplored. This project addresses that gap by investigating the dynamics of neurochemical signaling from Tregs. Prior studies have shown that these neurochemicals can influence Treg function, suggesting a potential therapeutic approach for neurological disorders. Methods To characterize real-time neurochemical signaling from Tregs, we used fast scan cyclic voltammetry (FSCV) which offers excellent temporal and spatial resolution. The study also investigated activation-mediated neurochemical secretion on this timescale using both artificial and biological activators including ionomycin, phytohemagglutinin-L (PHA-L), and interferon-beta (IFN-β). To validate the FSCV findings, we used mass spectrometry for neurochemical identification, qPCR for gene expression analysis, and flow cytometry to assess the phenotype and activation state. Results Our findings demonstrated the first sub-second release of neurochemicals from in vitro cultures of Tregs, revealing the neuronal-like dynamics and providing insight into how different activation pathways influence sub-second neurochemical signaling. Conclusion This work establishes a framework for connecting sub-second neurochemicals fluctuations to changes in Treg activation, expands the current paradigm of immune regulation and lays the foundation for therapeutic targeting of neuroimmune interactions. Funding Source NIH R21AG086735 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)