Pancreatic nerve electrostimulation inhibits recent-onset autoimmune diabetes

• Published in: Nature biotechnology Vol. 37; no. 12; pp. 1446 - 1451
• Main Authors: Guyot, Mélanie, Simon, Thomas, Ceppo, Franck, Panzolini, Clara, Guyon, Alice, Lavergne, Julien, Murris, Emilie, Daoudlarian, Douglas, Brusini, Romain, Zarif, Hadi, Abélanet, Sophie, Hugues-Ascery, Sandrine, Divoux, Jean-Louis, Lewis, Stephen J, Sridhar, Arun, Glaichenhaus, Nicolas, Blancou, Philippe
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.12.2019
• Subjects: Adrenergic receptors; Animals; Arthritis; Autoimmune diseases; Autoimmunity; B cells; B-Lymphocytes - immunology; Beta cells; Blood Glucose - metabolism; Cell proliferation; Cytokines; Cytokines - metabolism; Development and progression; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - therapy; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - therapy; Diabetes therapy; Electric Stimulation Therapy; Electrical stimuli; Female; Immune system; Inflammation; Insulin - metabolism; Life Sciences; Lipopolysaccharides; Lymph nodes; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Mitogens; Nerves; Pancreas; Pancreas - immunology; Pancreas - innervation; Pancreas - metabolism; Rheumatoid arthritis; Rheumatoid factor; Stimulation; Surgical implants; T cells; T-Lymphocytes - immunology; Type 1 diabetes; Vagus nerve; T-cells; electrostimulation; autoimmune diabetes; cross-presentation; leukocyte 19 migration; inflammation 20
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/s41587-019-0295-8

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.