Vagus nerve stimulation can ameliorate autoimmune diseases such as rheumatoid arthritis by modulation of the immune system. Its efficacy for the treatment of type 1 diabetes has not been explored, in part because the nerves projecting to the pancreatic lymph nodes (pLNs) in mice are unmapped. Here, we map the nerve projecting to the pancreas and pLNs in mice and use a minimally invasive surgical procedure to implant micro-cuff electrodes onto the nerve. Pancreatic nerve electrical stimulation (PNES) resulted in β-adrenergic receptor-mediated-accumulation of B and T cells in pLNs and reduced production of pro-inflammatory cytokines following lipopolysaccharide stimulation. Autoreactive T cells showed reduced proliferation in pLNs of mice receiving PNES as compared to sham controls. In a spontaneous mouse model of autoimmune diabetes, PNES inhibited disease progression in diabetic mice.
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Datasets that support the findings of this study are available from the corresponding author upon reasonable request.
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This work was funded by a collaborative research grant from GlaxoSmithKline Bioelectronics R&D to P.B. This work was also supported by the LABEX SIGNALIFE (no. ANR-11-LABX-0028-01) and the FHU Oncoage.
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Guyot, M., Simon, T., Ceppo, F. et al. Pancreatic nerve electrostimulation inhibits recent-onset autoimmune diabetes. Nat Biotechnol 37, 1446–1451 (2019) doi:10.1038/s41587-019-0295-8