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胰腺神经电刺激抑制近期发病的自身免疫性糖尿病。

Pancreatic nerve electrostimulation inhibits recent-onset autoimmune diabetes.

机构信息

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

E-PHY-SCIENCE, Valbonne, France.

出版信息

Nat Biotechnol. 2019 Dec;37(12):1446-1451. doi: 10.1038/s41587-019-0295-8. Epub 2019 Nov 11.

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.

摘要

迷走神经刺激通过调节免疫系统可以改善类风湿性关节炎等自身免疫性疾病。其治疗 1 型糖尿病的疗效尚未得到探索,部分原因是投射到小鼠胰腺淋巴结 (pLN) 的神经尚未被映射。在这里,我们绘制了投射到小鼠胰腺和 pLN 的神经图谱,并使用微创外科手术将微袖套电极植入神经上。胰腺神经电刺激 (PNES) 导致β肾上腺素能受体介导的 B 和 T 细胞在 pLN 中的积累,并减少脂多糖刺激后的促炎细胞因子的产生。与假手术对照组相比,接受 PNES 的小鼠的自身反应性 T 细胞在 pLN 中的增殖减少。在自身免疫性糖尿病的自发性小鼠模型中,PNES 抑制了糖尿病小鼠的疾病进展。

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