Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, 751 85, Uppsala, Sweden.
Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
Acta Diabetol. 2024 Sep;61(9):1117-1127. doi: 10.1007/s00592-024-02286-1. Epub 2024 May 8.
AIMS/HYPOTHESIS: Defensins play a crucial role in the innate immune system's first defense against microbial threats. However, little is known about the defensin system in the pancreas, especially in relation to Type 1 diabetes. We explore the expression of defensins in different disease stages of Type 1 diabetes and correlated obtained findings to the degree of inflammation, providing new insights into the disease and the innate immune system.
Pancreases from non-diabetic human organ donors of different age groups and donors with Type 1 diabetes with different disease duration were examined. Sections from head, body and tail of the pancreas were stained for eight different defensins and for immune cells; CD3+, CD45+, CD68+ and NES+ (granulocytes).
In non-diabetic adult controls the level of expression for defensins Beta-1,Alpha-1, Cathelicidin and REG3A correlated with the level of inflammation. In contrast, individuals with Type 1 diabetes exhibit a reduction or absence of several central defensins regardless of the level of inflammation in their pancreas. The expression of Cathelicidin is present in neutrophils and macrophages but not in T-cells in subjects with Type 1 diabetes.
Obtained findings suggest a pancreatic dysfunction in the innate immune system and the bridging to the adaptive system in Type 1 diabetes. Further studies on the role of the local innate immune system in Type 1 diabetes is needed.
目的/假设：防御素在先天免疫系统抵御微生物威胁的第一道防线中起着至关重要的作用。然而，人们对胰腺中的防御素系统知之甚少，特别是与 1 型糖尿病相关的防御素系统。我们研究了 1 型糖尿病不同疾病阶段防御素的表达情况，并将相关发现与炎症程度相关联，为该疾病和先天免疫系统提供新的见解。
检查了来自不同年龄组的非糖尿病人类器官供体和不同病程的 1 型糖尿病供体的胰腺。对胰腺头部、体部和尾部的组织切片进行了 8 种不同防御素和免疫细胞（CD3+、CD45+、CD68+和 NES+（粒细胞））的染色。
在非糖尿病成年对照组中，防御素 Beta-1、Alpha-1、Cathelicidin 和 REG3A 的表达水平与炎症水平相关。相比之下，1 型糖尿病患者的几种中心防御素的表达减少或缺失，而不论其胰腺炎症程度如何。Cathelicidin 在 1 型糖尿病患者的中性粒细胞和巨噬细胞中存在，但在 T 细胞中不存在。
研究结果表明 1 型糖尿病患者的先天免疫系统存在胰腺功能障碍，并与适应性免疫系统相连接。需要进一步研究局部先天免疫系统在 1 型糖尿病中的作用。
