β-Adrenergic receptors as immunomodulators in T cells: mechanisms of neuroimmune crosstalk and pathophysiological...

Regulation of T cell function by the sympathetic nervous system via β-adrenergic receptors is a pivotal research focus in neuroimmunology, with most studies centered on β₂-adrenergic receptors. However, the roles of other subtypes remain unclear. This review systematically summarizes differential expression and signaling of β₂- and β₁-adrenergic receptors across T cell subsets. While β₂-adrenergic receptor bidirectionally modulates immune responsiveness through classical or non-classical pathways, β₁-adrenergic receptor is predominantly expressed in regulatory and exhausted T cells, exerting immunosuppression via the cAMP-CREM axis. Furthermore, this review examines the pathophysiological roles of β-adrenergic receptor signaling in the tumor immune microenvironment, autoimmune diseases, infections and cardiovascular diseases, highlighting β₁-adrenergic receptor as a candidate immune checkpoint. Ultimately, elucidating the subtype-specific mechanisms of β-adrenergic signaling provides a critical framework for understanding immune dysregulation and highlights the potential of targeting these pathways to restore immune homeostasis in various pathological contexts.