Laboratory of Immunobiology for Research and Applications to Diagnosis (LIRAD), Research Institute Germans Trias i Pujol, Badalona, Spain.
Clin Exp Immunol. 2010 Jan;159(1):23-44. doi: 10.1111/j.1365-2249.2009.04053.x. Epub 2009 Nov 11.
Type 1 diabetes (T1D) is caused by the selective destruction of the insulin-producing beta cells of the pancreas by an autoimmune response. Due to ethical and practical difficulties, the features of the destructive process are known from a small number of observations, and transcriptomic data are remarkably missing. Here we report whole genome transcript analysis validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and correlated with immunohistological observations for four T1D pancreases (collected 5 days, 9 months, 8 and 10 years after diagnosis) and for purified islets from two of them. Collectively, the expression profile of immune response and inflammatory genes confirmed the current views on the immunopathogenesis of diabetes and showed similarities with other autoimmune diseases; for example, an interferon signature was detected. The data also supported the concept that the autoimmune process is maintained and balanced partially by regeneration and regulatory pathway activation, e.g. non-classical class I human leucocyte antigen and leucocyte immunoglobulin-like receptor, subfamily B1 (LILRB1). Changes in gene expression in islets were confined mainly to endocrine and neural genes, some of which are T1D autoantigens. By contrast, these islets showed only a few overexpressed immune system genes, among which bioinformatic analysis pointed to chemokine (C-C motif) receptor 5 (CCR5) and chemokine (CXC motif) receptor 4) (CXCR4) chemokine pathway activation. Remarkably, the expression of genes of innate immunity, complement, chemokines, immunoglobulin and regeneration genes was maintained or even increased in the long-standing cases. Transcriptomic data favour the view that T1D is caused by a chronic inflammatory process with a strong participation of innate immunity that progresses in spite of the regulatory and regenerative mechanisms.
1 型糖尿病（T1D）是由自身免疫反应引起的胰腺胰岛素产生β细胞的选择性破坏引起的。由于伦理和实际困难，破坏性过程的特征仅从少数观察中得知，并且转录组数据明显缺失。在这里，我们报告了全基因组转录分析，该分析通过定量逆转录-聚合酶链反应（qRT-PCR）进行了验证，并与来自四个 T1D 胰腺的免疫组织学观察结果相关（分别在诊断后 5 天，9 个月，8 年和 10 年收集），并与其中两个的纯化胰岛相关。总的来说，免疫反应和炎症基因的表达谱证实了当前对糖尿病免疫发病机制的看法，并与其他自身免疫性疾病具有相似性；例如，检测到干扰素特征。该数据还支持这样的概念，即自身免疫过程部分通过再生和调节途径的激活（例如非经典 I 类人白细胞抗原和白细胞免疫球蛋白样受体亚家族 B1（LILRB1））得以维持和平衡。胰岛中基因表达的变化主要局限于内分泌和神经基因，其中一些是 T1D 自身抗原。相比之下，这些胰岛仅显示少数过表达的免疫系统基因，其中生物信息学分析指出趋化因子（C-C 基序）受体 5（CCR5）和趋化因子（CXC 基序）受体 4（CXCR4）趋化因子途径激活。值得注意的是，固有免疫，补体，趋化因子，免疫球蛋白和再生基因的表达在长期病例中保持甚至增加。转录组数据支持 T1D 是由慢性炎症过程引起的观点，该过程具有先天免疫的强烈参与，尽管存在调节和再生机制，但仍在进展。
