Neurogenic Vasoactive Intestinal Peptide alters TCR proximal signaling in naive T cells 4007

Abstract Description Neuropeptides, such as vasoactive intestinal peptide (VIP), have emerged as key neuroimmune modulators that regulate lymphocyte function. In mouse models, transcriptomic profiling revealed that peripheral T cells express 26 neurotransmitter receptors, with distinct expression patterns across subsets. Notably, the VIP receptor, VIPR1, is highly expressed in naïve peripheral CD4 T cells but absent in regulatory T cells. Upon T cell receptor (TCR) engagement, VIPR1 expression rapidly diminishes, suggesting that endogenous VIP predominantly influences resting naïve T cells. Functionally, exogenous VIP attenuates early T cell activation by reducing proliferation and IL-2 production in response to antigenic stimulation. Mechanistic analysis revealed that while early proximal signaling events, such as ZAP70 phosphorylation, remain intact, VIP exposure significantly impairs downstream ERK activation. Given the short half-life of VIP, we hypothesize that localized neuronal production is a key determinant of its immunomodulatory effects. Through utilization of VIP lineage-tracing mice model, preliminary findings indicate robust VIP expression in neuronal populations within secondary lymphoid organs. Collectively, these data identify a neuroimmune axis through which neuronal VIP modulates naïve T cell activation during the early phases of the immune response, with implications for understanding tissue-specific immune regulation. Topic Categories Neuroimmunology (NEUR)