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<p>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 β<sub>2</sub>-adrenergic receptors. However, the roles of other subtypes remain unclear. This review systematically summarizes differential expression and signaling of β<sub>2</sub>- and β<sub>1</sub>-adrenergic receptors across T cell subsets. While β<sub>2</sub>-adrenergic receptor bidirectionally modulates immune responsiveness through classical or non-classical pathways, β<sub>1</sub>-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 β<sub>1</sub>-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.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Junyan Yao,
  • Suli Zhang,
  • Fei Sun,
  • Mingyang Chen,
  • Huirong Liu

摘要

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.

Graphical abstract