Interference with pancreatic sympathetic signaling halts the onset of diabetes in mice.

Christoffersson G, Ratliff SS, von Herrath MG

Sci Adv 6 (35) eabb2878 [2020-08-00; online 2020-08-26]

The notably lobular distribution of immune lesions in type 1 diabetes (T1D) has been hypothesized to be the result of innervation within the pancreas. To investigate whether neuroimmune interactions could explain this phenomenon, we explored the impact of sympathetic signaling in the RIP-LCMV-GP mouse model of autoimmune diabetes. In this model, the CD8+ T cell attack on β cells replicates a key pathogenic feature of human T1D. We found that inhibition of α1 adrenoceptors, ablation of sympathetic nerves, and surgical denervation all had a protective effect in this model, without affecting the systemic presence of β cell-reactive CD8+ T cells. In vivo multiphoton imaging revealed a local effect within pancreatic islets including limited infiltration of both macrophages and β cell-specific CD8+ T cells. Islet-resident macrophages expressed adrenoceptors and were responsive to catecholamines. Islet macrophages may therefore constitute a pivotal neuroimmune signaling relay and could be a target for future interventions in T1D.

Gustaf Christoffersson

SciLifeLab Fellow

PubMed 33052874

DOI 10.1126/sciadv.abb2878

Crossref 10.1126/sciadv.abb2878

pii: 6/35/eabb2878
pmc: PMC7531904

Publications 9.5.0