Endocrine Genetics, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
Mol Immunol. 2013 Dec;56(4):804-10. doi: 10.1016/j.molimm.2013.07.015. Epub 2013 Aug 23.
Type 1 diabetes is an autoimmune disease resulting from the destruction of pancreatic beta-cells. One of the main antigens targeted in this auto reactive response is insulin. It has been shown that insulin is expressed in small amounts in the thymus, and more specifically in the medullary thymic epithelial cells (mTECs), which also express a variety of other tissue-specific antigens. This thymic expression enables the maintenance of self-tolerance, and is essential in preventing auto-immune disease. Our laboratory has created a mouse mTEC clonal cell line specifically expressing insulin in order to better understand the regulatory mechanisms of this ectopic expression of insulin. In this study, we compared the insulin expressing cell line to an insulin non-expressing mTEC line by genome-wide expression profiling.
The most important difference was overexpression of CD34 in the insulin expressing clone, confirmed by Real-time Rt-PCR and flow cytometry. Cells in the thymus expressing higher levels of CD34 were found to contain higher levels of insulin and, to a lesser extent, Aire, a master regulator of self-antigen expression in the thymus. The cells expressing CD34 were not enriched in CD80, a known mTEC maturity marker.
CD34 may be a specific marker for functionality, with some specificity for insulin.
1 型糖尿病是一种自身免疫性疾病，由胰腺β细胞的破坏引起。在这种自身反应中，主要的靶抗原之一是胰岛素。已经表明，胰岛素在胸腺中以少量表达，特别是在髓质胸腺上皮细胞（mTEC）中，mTEC 还表达多种其他组织特异性抗原。这种胸腺表达使自身耐受得以维持，对于预防自身免疫性疾病至关重要。我们的实验室已经创建了一种特异性表达胰岛素的小鼠 mTEC 克隆细胞系，以更好地理解这种胰岛素异位表达的调节机制。在这项研究中，我们通过全基因组表达谱分析比较了表达胰岛素的细胞系和不表达胰岛素的 mTEC 系。
在胰岛素表达克隆中，CD34 的过度表达是最重要的差异，这通过实时 RT-PCR 和流式细胞术得到了证实。在胸腺中表达更高水平 CD34 的细胞被发现含有更高水平的胰岛素，在较小程度上含有 Aire，Aire 是胸腺中自身抗原表达的主要调节因子。表达 CD34 的细胞并未富集 CD80，CD80 是已知的 mTEC 成熟标志物。
CD34 可能是功能的特异性标志物，对胰岛素具有一定的特异性。
