Purpose

IL-17 is an important effector cytokine driving immune-mediated destruction in autoimmune diseases such as psoriasis. Blockade of the IL-17 pathway after the initiation of insulitis was effective in delaying or preventing the onset of type 1 diabetes (T1D) in rodent models. Expression of IL-17 transcripts in islets from a donor with recent-onset T1D has been reported, however, studies regarding IL-17 protein expression are lacking. We aimed to study whether IL-17 is being expressed in the islets of diabetic donors.

Methods

We stained human pancreatic tissues from non-diabetic (n = 5), auto-antibody positive (aab+) (n = 5), T1D (n = 6) and T2D (n = 5) donors for IL-17, Insulin, and Glucagon, and for CD45 in selected cases. High resolution images were acquired with Zeiss laser scanning confocal microscope LSM780 and analyzed with Zen blue 2.3 software. Cases stained for CD45 were also acquired with widefield slide scanner and analyzed with QuPath software.

Results

We observed a clear cytoplasmic staining for IL-17 in insulin-containing islets of donors with T1D and T2D, accounting for an average of 7.8 ± 8.4% and 14.9 ± 16.8% of total islet area, respectively. Both beta and alpha cells were sources of IL-17, but CD45⁺ cells were not a major source of IL-17 in those donors. Expression of IL-17 was reduced in islets of non-diabetic donors, aab+ donors and in insulin-deficient islets of donors with T1D.

Conclusion

Our finding that IL-17 is expressed in islets of donors with T1D or T2D is quite intriguing and warrants further mechanistic studies in human islets to understand the role of IL-17 in the context of metabolic and immune stress in beta cells.

中文翻译：

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IL-17 在 1 型和 2 型糖尿病供体的 β 和 α 细胞上表达

目的

IL-17 是一种重要的效应细胞因子，在银屑病等自身免疫性疾病中驱动免疫介导的破坏。在啮齿动物模型中，胰岛炎开始后阻断 IL-17 通路可有效延缓或预防 1 型糖尿病 (T1D) 的发作。据报道，近期发病的 T1D 供体胰岛中 IL-17 转录物的表达，然而，缺乏关于 IL-17 蛋白表达的研究。我们旨在研究 IL-17 是否在糖尿病供体的胰岛中表达。

方法

我们对来自非糖尿病 (n = 5)、自身抗体阳性 (aab+) (n = 5)、T1D (n = 6) 和 T2D (n = 5) 供体的人胰腺组织进行 IL-17、胰岛素和胰高血糖素，在特定病例中用于 CD45。使用蔡司激光扫描共聚焦显微镜 LSM780 获得高分辨率图像，并使用 Zen blue 2.3 软件进行分析。CD45 染色的病例也用广角玻片扫描仪采集，并用 QuPath 软件进行分析。

结果

我们观察到 T1D 和 T2D 供体的含胰岛素胰岛中 IL-17 的细胞质染色清晰，平均分别占胰岛总面积的 7.8 ± 8.4% 和 14.9 ± 16.8%。β 和 α 细胞都是 IL-17 的来源，但 CD45 ⁺细胞不是这些供体中 IL-17 的主要来源。IL-17 的表达在非糖尿病供体、aab+ 供体的胰岛和 T1D 供体的胰岛素缺乏胰岛中的表达降低。

结论

我们发现 IL-17 在 T1D 或 T2D 供体的胰岛中表达非常有趣，需要在人类胰岛中进行进一步的机制研究，以了解 IL-17 在 β 细胞代谢和免疫应激背景下的作用。