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Diabetologia:胰岛中透明质酸的沉积可能先于并引导胰岛免疫细胞浸润位置

2020-04-12 MedSci原创 MedSci原创

透明质酸(HA)的大量沉积是显性1型糖尿病的特征。我们研究了在疾病发生的早期在胰岛中是否可检测到HA积累,以及这如何影响胰岛炎和β细胞团的发展。

透明质酸(HA)的大量沉积是显性1型糖尿病的特征。我们研究了在疾病发生的早期在胰岛中是否可检测到HA积累,以及这如何影响胰岛炎和β细胞团的发展。

研究人员对15例胰岛自身抗体(aAb)阳性的非糖尿病器官供体和14例同样年龄的aAb对照供体的胰腺组织进行胰岛HA染色量和肌炎的检查。在DRLyp/Lyp大鼠(一种自发性自身免疫性糖尿病模型)中,从40天到糖尿病发作,研究了胰岛HA沉积动力学、insulitis的发病和进展以及细胞质量的变化。

在3例单抗和4例双aAb+供体(aAb+HAhigh)的胰腺组织中观察到丰富的胰岛HA沉积。在这7个组织中,HA染色的面积在小鼠的小鼠体内测量1000±240μm2(平均±SEM),并比aAb-对照组组织中的面积大4倍。aAb+HA高组织也有更大的发病率,是高度丰富的HA(21%的这些组织中的小鼠组织中含有最大的HA染色区域[>2000μm2]与不到1%的组织从aAb-对照供体的组织)。胰岛HA染色量与单株或双株抗体阳性数相关,在这些组织中HA染色的量与aAb的数量有关(即单Ab或双Ab阳性),但与HLA基因型或β细胞质量的变化无关。在7个aAb+HA高的组织中,3个来自单aAb+供体和1个来自双aAb+供体的组织中没有显示出任何小鼠免疫细胞浸润,表明HA在aAb+供体中的积累与胰岛炎无关。3个aAb+HA高的组织表现为胰岛炎,其中3个aAb+HA高的组织有最大的HA浸润面积,而且在这些组织中,小鼠移植免疫细胞与最突出的HA沉积物共同定位(即HA浸润面积>2000 μm2)。在7-8周龄的无症状前DRLyp/Lyp大鼠中,在小鼠的小鼠HA的积累是明显的,其中小鼠的小鼠HA染色面积测量2370±170μm2(平均±SEM),这是在6周龄大鼠的三倍。这种最初的小鼠HA沉积并不与β细胞丢失同时发生。在9-10周龄的大鼠中,首次检测到胰岛炎,其中HA染色面积为4980±500μm2。在这个年龄,大鼠还表现出β细胞质量减少44%。进一步扩大的HA阳性区域(平均±SEM:7220±880μm2)与侵袭性胰岛炎有关。HA沉积物在破坏性肾小管炎的大鼠的肾小管中仍有丰富的沉积物,其中85%的β细胞丢失。

本研究表明,HA沉积于胰岛早于1型糖尿病,早于胰岛炎,并提示HA可能触发胰岛免疫细胞浸润,促进胰岛炎。

原始出处:

Marika Bogdani, Cate Speake,Hyaluronan deposition in islets may precede and direct the location of islet immune-cell infiltrates

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    2020-09-15 baoya
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