Helminen Olli, Huhta Heikki, Kauppila Joonas H, Lehenkari Petri P, Saarnio Juha, Karttunen Tuomo J
Department of Pathology, University of Oulu, Oulu, Finland.
Department of Surgery, University of Oulu, Oulu, Finland.
APMIS. 2017 Feb;125(2):85-92. doi: 10.1111/apm.12632. Epub 2016 Dec 28.
Nucleic acid-sensing toll-like receptors (TLRs) (3, 7, 8, 9) have a role both in antiviral innate immunity and in autoimmune disorders. We assessed the expression of TLR3, 7, 8 and 9 in human and mouse pancreas focusing on the subpopulations of cells in the Langerhans islets. We studied eight human samples with normal pancreatic islets and two samples from patients with type 1 diabetes. Additionally, 10 CD-1 mouse pancreases were analysed. Immunohistochemical double-stainings for the TLRs and insulin, glucagon or somatostatin, respectively, were performed along with appropriate controls. In human pancreas, strong immunoreaction of TLR7 and TLR8 was observed in the insulin-positive beta cells, whereas glucagon- or somatostatin-expressing cells of the islets were weakly stained or negative. In type 1 diabetes, the expression in islets was weak or lost (TLR7: p = 0.014, TLR8: p = 0.053), correlating with loss of beta cells. TLR3 and 9 were expressed only weakly with no correlation with specific cell types. In mouse pancreas, only TLR9 was detected. Intra-pancreatic nerve ganglia strongly expressed TLR7. The strong expression of TLR7 and TLR8 in the beta cells of normal human islets could be an important piece in the puzzle of type 1 diabetes pathogenesis, and be linked with destruction of this particular subpopulation of the islet cells. In normal mice, only TLR9 can be constantly detected in the islets, highlighting differences between the species.
核酸传感Toll样受体（TLRs）（3、7、8、9）在抗病毒天然免疫和自身免疫性疾病中均发挥作用。我们评估了TLR3、7、8和9在人和小鼠胰腺中的表达，重点关注胰岛中的细胞亚群。我们研究了8例具有正常胰岛的人类样本和2例1型糖尿病患者的样本。此外，还分析了10个CD-1小鼠的胰腺。分别对TLRs与胰岛素、胰高血糖素或生长抑素进行免疫组织化学双重染色，并设置适当的对照。在人类胰腺中，TLR7和TLR8在胰岛素阳性的β细胞中观察到强烈的免疫反应，而胰岛中表达胰高血糖素或生长抑素的细胞染色较弱或呈阴性。在1型糖尿病中，胰岛中的表达较弱或缺失（TLR7：p = 0.014，TLR8：p = 0.053），与β细胞的丧失相关。TLR3和9仅微弱表达，与特定细胞类型无相关性。在小鼠胰腺中，仅检测到TLR9。胰腺内神经节强烈表达TLR7。正常人类胰岛β细胞中TLR7和TLR8的强烈表达可能是1型糖尿病发病机制难题中的重要一环，并与胰岛细胞这一特定亚群的破坏有关。在正常小鼠中，胰岛中只能持续检测到TLR9，突出了物种之间的差异。
