Centre for Human Immunology, Department of Microbiology and Immunology and Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
J Interferon Cytokine Res. 2011 Oct;31(10):711-9. doi: 10.1089/jir.2011.0025. Epub 2011 Aug 18.
Juvenile or type 1 diabetes (T1D) involves autoimmune-mediated destruction of insulin-producing β cells in the islets of Langerhans in the pancreas. Lack of insulin prevents the absorption and metabolism of glucose throughout the body by interfering with cell signaling. Cytokines have been shown to play a key role in β cell destruction and regulation of autoimmunity in T1D. The multiple roles of cytokines in T1D pathogenesis, regulation, and regeneration of β cells presents both promise and challenge for their use in immunotherapy. We found that mycobacterial adjuvants induce various regulatory T cells in the non-obese diabetic (NOD) mouse model of T1D. Cytokines produced by these cells not only regulate innate and adaptive immunity but also prevent the development of diabetes and partially restored normoglycemia in diabetic NOD mice. We discovered that adjuvant immunotherapy upregulated Regenerating (Reg) genes in the islets and induced interleukin 22 (IL-22)-producing Th17 cells. IL-22 is known to upregulate Reg gene expression in islets and could potentially induce regeneration of β cells and prevent their apoptosis. Therefore, cytokines both induce and regulate T1D and have the potential to regenerate and preserve insulin-producing β cells in the islets.
青少年或 1 型糖尿病（T1D）涉及胰岛β细胞的自身免疫性破坏，胰岛β细胞是胰腺中产生胰岛素的细胞。缺乏胰岛素会通过干扰细胞信号传导，阻止全身对葡萄糖的吸收和代谢。细胞因子已被证明在β细胞破坏和 T1D 自身免疫调节中发挥关键作用。细胞因子在 T1D 发病机制、β细胞调节和再生中的多种作用，为其在免疫治疗中的应用既带来了希望，也带来了挑战。我们发现分枝杆菌佐剂在 T1D 的非肥胖型糖尿病（NOD）小鼠模型中诱导产生各种调节性 T 细胞。这些细胞产生的细胞因子不仅调节先天和适应性免疫，而且还可以预防糖尿病的发生，并使糖尿病 NOD 小鼠的血糖部分恢复正常。我们发现佐剂免疫治疗可上调胰岛中的再生（Reg）基因，并诱导产生白细胞介素 22（IL-22）的 Th17 细胞。已知白细胞介素 22 可上调胰岛中 Reg 基因的表达，并可能诱导β细胞的再生并防止其凋亡。因此，细胞因子既能诱导又能调节 T1D，并且具有在胰岛中再生和保存产生胰岛素的β细胞的潜力。
