Buschard Karsten, Krogvold Lars, Pociot Flemming, Gerling Ivan, Thea Rikke, Dahl-Jørgensen Knut, Hansen Camilla Hartmann Friis
The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen, Denmark
Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg Campus, Frederiksberg, Denmark.
BMJ Open Diabetes Res Care. 2025 Sep 5;13(5):e005111. doi: 10.1136/bmjdrc-2025-005111.
In mammalian and human life, it is important that the immune system defends against microorganisms. Although there is a huge overlap, innate cells are good against bacteria, whereas T cells are good against viruses, mainly because of antibody production via T helper and B lymphocytes. Toll-like receptor 5 (TLR5) is a regulator; when it is highly expressed, T cells are inhibited, and innate cells are favored. In glucose-activated pancreatic islets, gene expression has been found to be highly upregulated, and the islets may therefore be protected from T cell destruction resulting in autoimmune type 1 diabetes (T1D).
We investigated mRNA from the islets of Langerhans in patients with newly diagnosed T1D for gene expression, as well as and expression in the whole pancreatic tissue of female diabetic non-obese diabetic (NOD) mice. Also, we examined for polymorphisms between , immunological parameters, and T1D.
Islet mRNA for was downregulated by one-third of patients with newly diagnosed T1D, compared with controls, and correlated inversely with T cell infiltration in the islets. Moreover, the association between TLR5 and T cells was supported by a corresponding correlation of and expression in the pancreatic tissue of diabetic NOD mice. Regarding polymorphisms, two associations were found between and monocytes. Also, a significant polymorphism was seen concerning and T1D.
In the present study, we find a low expression of mRNA for in patients with newly diagnosed T1D associated with enhanced T cell infiltration. T cells are important for autoimmune diseases, including T1D. We hope that the present findings may be influential for the understanding of how T1D develops.
在哺乳动物和人类生命中，免疫系统抵御微生物至关重要。尽管存在大量重叠，但固有细胞对细菌有良好的抵御作用，而T细胞对病毒有良好的抵御作用，这主要是因为通过辅助性T细胞和B淋巴细胞产生抗体。Toll样受体5（TLR5）是一种调节因子；当它高表达时，T细胞受到抑制，固有细胞则受到青睐。在葡萄糖激活的胰岛中，已发现该基因表达高度上调，因此胰岛可能受到保护，免受导致自身免疫性1型糖尿病（T1D）的T细胞破坏。
我们调查了新诊断T1D患者胰岛中该基因的mRNA表达，以及雌性糖尿病非肥胖糖尿病（NOD）小鼠整个胰腺组织中的该基因和另一基因的表达。此外，我们还检测了该基因的多态性、免疫参数与T1D之间的关系。
与对照组相比，新诊断T1D患者中有三分之一的胰岛mRNA表达下调，且与胰岛中的T细胞浸润呈负相关。此外，糖尿病NOD小鼠胰腺组织中该基因和另一基因表达的相应相关性支持了TLR5与T细胞之间的关联。关于多态性，在该基因与单核细胞之间发现了两种关联。此外，在该基因与T1D之间也发现了显著的多态性。
在本研究中，我们发现新诊断T1D患者中该基因的mRNA表达较低，这与T细胞浸润增强有关。T细胞对包括T1D在内的自身免疫性疾病很重要。我们希望本研究结果可能对理解T1D的发病机制有一定影响。
