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Interference with p...
Interference with pancreatic sympathetic signaling halts the onset of diabetes in mice
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- Christoffersson, Gustaf (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Science for Life Laboratory, SciLifeLab,La Jolla Inst Immunol, La Jolla, CA 92037 USA
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- Ratliff, Sowbarnika S. (författare)
- La Jolla Inst Immunol, La Jolla, CA 92037 USA.
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- von Herrath, Matthias G. (författare)
- La Jolla Inst Immunol, La Jolla, CA 92037 USA.;Novo Nordisk Res Ctr, Seattle, WA 98109 USA.
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2020
- 2020
- Engelska.
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:35
- Relaterad länk:
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https://advances.sci...
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visa fler...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 beta cells replicates a key pathogenic feature of human T1D. We found that inhibition of alpha(1) adrenoceptors, ablation of sympathetic nerves, and surgical denervation all had a protective effect in this model, without affecting the systemic presence of beta cell-reactive CD8(+) T cells. In vivo multiphoton imaging revealed a local effect within pancreatic islets including limited infiltration of both macrophages and beta 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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