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Pancreatic nerve electrostimulation inhibits recent-onset autoimmune diabetes

Nature Biotechnology volume 37, pages 1446–1451 (2019)Cite this article

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Abstract

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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Fig. 1: Pancreatic nerve electrophysiological and functional characterization.
Fig. 2: Impact of PNES on immune cell number, cytokine production and T cell proliferation in pLNs.
Fig. 3: Impact of PNES on glycemia and insulitis in NOD mice.

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Data availability

Datasets that support the findings of this study are available from the corresponding author upon reasonable request.

Change history

  • 19 February 2020

    In the supplementary information originally posted for this article, characters were corrupted in the figure lettering. The error has been corrected online.

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Acknowledgements

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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Author notes

  1. These authors contributed equally: Mélanie Guyot, Thomas Simon.

Authors and Affiliations

  1. Université Côte d’Azur, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France

    Mélanie Guyot, Thomas Simon, Franck Ceppo, Clara Panzolini, Alice Guyon, Julien Lavergne, Emilie Murris, Douglas Daoudlarian, Romain Brusini, Hadi Zarif, Sophie Abélanet, Nicolas Glaichenhaus & Philippe Blancou

  2. E-PHY-SCIENCE, Valbonne, France

    Sandrine Hugues-Ascery

  3. AXONIC, Vallauris, France

    Jean-Louis Divoux

  4. Departments of Pediatrics and Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

    Stephen J. Lewis

  5. Galvani Bioelectronics, Stevenage, UK

    Arun Sridhar

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Contributions

P.B. conceived the study. M.G., T.S. and P.B. designed experiments. M.G., F.C., T.S., A.G., C.P., E.M., D.D., R.B., S.A., S.H-A., S.J.L. and P.B. performed experiments. M.G., F.C., T.S., A.G., A.S., N.G. and P.B. interpreted the data. S.J.L. helped to identify the location of the pancreatic nerve in mice. J.-L.D. provided one of the external stimulators used in this study. P.B. wrote the manuscript and N.G. edited the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Philippe Blancou.

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Supplementary Figs. 1–14.

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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). https://doi.org/10.1038/s41587-019-0295-8

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