Saito I, Haruta K, Shimuta M, Inoue H, Sakurai H, Yamada K, Ishimaru N, Higashiyama H, Sumida T, Ishida H, Suda T, Noda T, Hayashi Y, Tsubota K
Department of Pathology, Tokushima University School of Dentistry, Kuramotocho, Tokushima, Japan.
J Immunol. 1999 Mar 1;162(5):2488-94.
Although IL-10 has been implicated in the pathogenesis of several autoimmune diseases, the mechanisms by which this cytokine mediates inflammatory lesions remain to be elucidated. Exocrine gland destruction is an important early step in the development of Sjögren's syndrome. To better understand the role of IL-10 in Sjögren's syndrome, we made transgenic mice in which the mouse IL-10 gene was regulated by the human salivary amylase promoter. Transgenic expression of IL-10 induced apoptosis of glandular tissue destruction and lymphocyte infiltration consisting primarily of Fas-ligand (FasL)+ CD4+ T cells, as well as in vitro up-regulation of FasL expression on T cells. These data suggest that overexpression of IL-10 in the glands and their subsequent Fas/FasL-mediated bystander tissue destruction is a causal factor in the development of this disease.
尽管白细胞介素-10（IL-10）与多种自身免疫性疾病的发病机制有关，但这种细胞因子介导炎症损伤的机制仍有待阐明。外分泌腺破坏是干燥综合征发展过程中的一个重要早期步骤。为了更好地理解IL-10在干燥综合征中的作用，我们构建了转基因小鼠，其中小鼠IL-10基因由人唾液淀粉酶启动子调控。IL-10的转基因表达诱导了主要由Fas配体（FasL）+ CD4 + T细胞组成的腺组织破坏和淋巴细胞浸润的凋亡，以及T细胞上FasL表达的体外上调。这些数据表明，腺体中IL-10的过表达及其随后由Fas/FasL介导的旁观者组织破坏是该疾病发展的一个致病因素。
