IL-17 is expressed on beta and alpha cells of donors with type 1 and type 2 diabetes.
IL-17 is expressed on beta and alpha cells of donors with type 1 and type 2 diabetes.
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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。
DOI：
10.1016/j.jaut.2021.102708
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发表时间：
2021-09
影响因子：
12.8
通讯作者：
von Herrath M
中科院分区：
文献类型：
--
作者：
Rajendran S;Quesada-Masachs E;Zilberman S;Graef M;Kiosses WB;Chu T;Benkahla MA;Lee JM;von Herrath M
IL-17是一种重要的效应细胞因子，在自身免疫性疾病如银屑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通路可有效延迟或预防1型糖尿病（T1 D）的发作。已经报道了来自最近发作的T1 D供体的胰岛中IL-17转录物的表达，然而，缺乏关于IL-17蛋白表达的研究。我们的目的是研究IL-17是否在糖尿病供体的胰岛中表达。我们对来自非糖尿病（n=5）、自身抗体阳性（aab+）（n=5）、T1 D（n=6）和T2 D（n=5）供体的人胰腺组织进行了IL-17、胰岛素和胰高血糖素染色，并在选定病例中进行了CD 45染色。用Zeiss激光扫描共聚焦显微镜LSM 780获得高分辨率图像，并用Zen blue 2.3软件分析。CD 45染色的病例也用宽视野载玻片扫描仪获得，并用QuPath软件分析。我们在T1 D和T2 D供体的含胰岛素胰岛中观察到明显的IL-17胞浆染色，平均分别占总胰岛面积的7.8 ± 8.4%和14.9 ± 16.8%。β和α细胞都是IL-17的来源，但CD 45不是这些供体的主要来源。IL-17的表达在非糖尿病供体、aab+供体的胰岛和患有T1 D的供体的胰岛素缺乏胰岛中降低。我们发现IL-17在患有T1 D或T2 D的供体的胰岛中表达是非常有趣的，并且需要在人类胰岛中进行进一步的机制研究，以了解IL-17在代谢和免疫应激背景下的作用。
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. 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. 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 was not a major source 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. 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.
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影响因子：
13.2
作者：
Jin, Wei;Dong, Chen
通讯作者：
Dong, Chen
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
7.7
作者：
Ferraro A;Socci C;Stabilini A;Valle A;Monti P;Piemonti L;Nano R;Olek S;Maffi P;Scavini M;Secchi A;Staudacher C;Bonifacio E;Battaglia M
通讯作者：
Battaglia M
影响因子：
12.8
作者：
Anquetil F;Sabouri S;Thivolet C;Rodriguez-Calvo T;Zapardiel-Gonzalo J;Amirian N;Schneider D;Castillo E;Lajevardi Y;von Herrath MG
通讯作者：
von Herrath MG
影响因子：
7.7
作者：
Emamaullee JA;Davis J;Merani S;Toso C;Elliott JF;Thiesen A;Shapiro AM
通讯作者：
Shapiro AM