Publication date: Jun 24, 2026
The autonomic nervous system (ANS) plays a central role in immune homeostasis by integrating sympathetic and parasympathetic signals that regulate inflammation, immune cell trafficking, and tolerance. Aging is associated with a progressive autonomic imbalance characterized by sympathetic overactivation, reduced parasympathetic tone, and impaired β-adrenergic signaling in immune cells, which together contribute to inflammaging and immune dysregulation. In this review, we discuss how aging-related alterations in adrenergic pathways affect immune cell differentiation and cytokine networks, with particular emphasis on β₂-adrenergic control of the Th17/regulatory T cell balance through cAMP-dependent mechanisms interacting with cytokine-driven STAT signaling. Chronic sympathetic stimulation and β-adrenergic desensitization weaken these regulatory constraints, favoring pro-inflammatory immune trajectories and loss of immune tolerance. Finally, we propose Long COVID as a paradigmatic condition in which pre-existing inflammaging and autonomic vulnerability are amplified by viral infection, leading to persistent inflammation, impaired immune regulation, and increased susceptibility to autoimmune manifestations.
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| Concepts | Keywords |
|---|---|
| Autoimmune | Autoimmunity |
| Homeostasis | Autonomic nervous system |
| Nervous | Beta-adrenergic receptors |
| Pro | Long COVID |
| Viral | Th17 cells |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | long COVID |
| disease | MESH | inflammation |
| drug | DRUGBANK | Isoxaflutole |
| drug | DRUGBANK | Cyclic Adenosine Monophosphate |
| disease | MESH | viral infection |