Macrophages as Central Mediators of Sympathetic Neuro-Immune Interplay in Autoimmunity

This review discusses the critical role of sympathetic nerve-macrophage communication in maintaining tissue homeostasis and its disruption in autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, sarcoidosis, inflammatory bowel disease, and alopecia areata. Disturbances in this neuroimmune crosstalk, including loss of sympathetic innervation and altered catecholamine levels, contribute to autoimmune inflammation. Macrophages interact with sympathetic neurons through β₂-adrenergic receptor signaling and can modulate local inflammatory responses by acting as norepinephrine sinks. Reduced norepinephrine availability and impaired adrenergic signaling are linked to increased cytokine production and tissue damage. The review suggests that restoring neuroimmune communication through β-adrenergic modulation, macrophage-targeted therapies, or neuromodulation devices could be a promising therapeutic approach for autoimmune disorders, highlighting the need for further research into nerve-macrophage dynamics.