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Peer-reviewedCC BY 4.0Frontiers in Immunology

Immune cell β2-adrenergic receptor signaling in myocardial injury: from neuroimmune crosstalk to precision immunomodulation

  • Xiaolin Su1,2
  • Lin Li1
  • Weizhong Han1
  • Yan Hao1
  1. 1Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University
  2. 2Shandong First Medical University
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Abstract

The β2-adrenergic receptor (β2-AR), a G protein-coupled receptor widely expressed on immune cells, has emerged as an important regulator linking sympathetic activation with inflammatory responses during myocardial injury. Beyond its established cardiovascular functions, β2-AR orchestrates immune cell migration, polarization, cytokine production, and efferocytosis, thereby shaping the initiation, resolution, and repair phases of cardiac inflammation. Recent studies have identified several immune-specific mechanisms through which β2-AR regulates leukocyte trafficking via the VCAM-1 and CCR2 axes, influences Annexin A1-dependent efferocytosis, and undergoes functional reprogramming through GRK2- and β-arrestin-mediated signaling. These mechanisms highlight the dynamic and context-dependent nature of immune β2-AR signaling, while also helping to explain why therapeutic modulation of this pathway has shown inconsistent clinical efficacy despite encouraging experimental findings. Current therapeutic strategies include selective β-blockade and GRK2-targeted interventions, whereas emerging approaches such as immune cell-specific β2-AR restoration, βARKct gene delivery, and biomaterial-based pro-resolving therapies remain at the preclinical stage. This review summarizes the expression patterns, signaling mechanisms, and immunoregulatory functions of β2-AR in immune cells, discusses its context-dependent roles across myocardial infarction, ischemia/reperfusion injury, and heart failure, and highlights current translational challenges and future opportunities for precision immunomodulation targeting immune cell β2-AR signaling.

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Cite

BibTeXRIS
BibTeX
@article{su2026immune,
  title = {{Immune cell β2-adrenergic receptor signaling in myocardial injury: from neuroimmune crosstalk to precision immunomodulation}},
  author = {Xiaolin Su and Lin Li and Weizhong Han and Yan Hao},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1976748},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1976748/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Immune cell β2-adrenergic receptor signaling in myocardial injury: from neuroimmune crosstalk to precision immunomodulation
AU  - Xiaolin Su
AU  - Lin Li
AU  - Weizhong Han
AU  - Yan Hao
PY  - 2026
DA  - 2026/10/26
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1976748
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1976748/full
AB  - The β2-adrenergic receptor (β2-AR), a G protein-coupled receptor widely expressed on immune cells, has emerged as an important regulator linking sympathetic activation with inflammatory responses during myocardial injury. Beyond its established cardiovascular functions, β2-AR orchestrates immune cell migration, polarization, cytokine production, and efferocytosis, thereby shaping the initiation, resolution, and repair phases of cardiac inflammation. Recent studies have identified several immune-specific mechanisms through which β2-AR regulates leukocyte trafficking via the VCAM-1 and CCR2 axes, influences Annexin A1-dependent efferocytosis, and undergoes functional reprogramming through GRK2- and β-arrestin-mediated signaling. These mechanisms highlight the dynamic and context-dependent nature of immune β2-AR signaling, while also helping to explain why therapeutic modulation of this pathway has shown inconsistent clinical efficacy despite encouraging experimental findings. Current therapeutic strategies include selective β-blockade and GRK2-targeted interventions, whereas emerging approaches such as immune cell-specific β2-AR restoration, βARKct gene delivery, and biomaterial-based pro-resolving therapies remain at the preclinical stage. This review summarizes the expression patterns, signaling mechanisms, and immunoregulatory functions of β2-AR in immune cells, discusses its context-dependent roles across myocardial infarction, ischemia/reperfusion injury, and heart failure, and highlights current translational challenges and future opportunities for precision immunomodulation targeting immune cell β2-AR signaling.
SN  - 1664-3224
ER  -