Abstract Text: Neuromodulation has been proposed as a potential therapeutic option for autoimmune diseases. Indeed, the autonomic nervous system can inhibit inflammation via the binding of catecholamine and acetylcholine to their respective cognate receptors expressed by immune cells. Clinical studies showed that vagus nerve stimulation (VNS) can be beneficial for patients with rheumatoid arthritis and Crohn’s Disease. However, this approach lacked efficacy in some patients and VNS had adverse effects presumably because the vagus nerve contains both afferent and efferent fibers, which regulate the function of multiple organs. We hypothesized that applying electrical stimulation to exclusively efferent nerves proximal to target organs could potentially be a more efficacious and specific therapy. We tested the therapeutic efficacy of splenic nerve electrostimulation (SNES) in collagen-induced arthritis (CIA) and pancreatic nerve stimulation (PNES) in spontaneous type 1 diabetes (T1D) in mice. SNES treatment of CIA mice significantly reduced clinical scores compared to sham treated animals in a β- adrenergic receptor dependent manner. After SNES treatment, the numbers of autoantibody-secreting cells were reduced, as well as serum levels of TNF and anti-collagen antibodies. In a spontaneous mouse model of T1D, PNES inhibited disease progression in diabetic mice. PNES resulted in β-adrenergic receptor-mediated-accumulation of B and T cells in pancreatic lymph nodes (pLNs) and reduced production of pro-inflammatory cytokines. Autoreactive T cells showed reduced proliferation in pLNs of mice receiving PNES as compared to sham controls. In conclusion, our findings provide a rationale to further explore peripheral nerve neuromodulation as a treatment for autoimmune diseases.
