La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Department of Medical Cell Biology, Uppsala University, Uppsala 75237, Sweden.
Sci Adv. 2020 Aug 26;6(35). doi: 10.1126/sciadv.abb2878. Print 2020 Aug.
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 α 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.
1 型糖尿病（T1D）中免疫病变的明显小叶分布，据推测是胰腺内神经支配的结果。为了探究神经免疫相互作用是否可以解释这一现象，我们研究了在自身免疫性糖尿病的 RIP-LCMV-GP 小鼠模型中交感神经信号的影响。在该模型中，CD8 T 细胞对β细胞的攻击复制了人类 T1D 的一个关键致病特征。我们发现，α肾上腺素能受体抑制、交感神经消融和手术去神经支配在该模型中均具有保护作用，而不影响β细胞反应性 CD8 T 细胞的全身存在。体内多光子成像显示了胰岛内的局部效应，包括巨噬细胞和β细胞特异性 CD8 T 细胞的有限浸润。胰岛驻留巨噬细胞表达肾上腺素能受体并对儿茶酚胺有反应。因此，胰岛巨噬细胞可能构成一个关键的神经免疫信号转导中继，并可能成为 T1D 未来干预的靶点。
