Stewart T A, Hultgren B, Huang X, Pitts-Meek S, Hully J, MacLachlan N J
Department of Endocrine Research, Genentech, Inc., South San Francisco, CA 94080.
Science. 1993 Jun 25;260(5116):1942-6. doi: 10.1126/science.8100367.
Type I diabetes is an autoimmune disease involving an interaction between an epigenetic event (possibly a viral infection), the pancreatic beta cells, and the immune system in a genetically susceptible host. The possibility that the type I interferons could mediate this interaction was tested with transgenic mice in which the insulin-producing beta cells expressed an interferon-alpha. These mice developed a hypoinsulinemic diabetes associated with a mixed inflammation centered on the islets. The inflammation and the diabetes were prevented with a neutralizing antibody to the interferon-alpha. Thus, the expression of interferon-alpha by the beta cells could be causal in the development of type I diabetes, which suggests a therapeutic approach to this disease.
1型糖尿病是一种自身免疫性疾病，涉及表观遗传事件（可能是病毒感染）、胰腺β细胞和遗传易感宿主免疫系统之间的相互作用。通过转基因小鼠对I型干扰素介导这种相互作用的可能性进行了测试，在这些转基因小鼠中，产生胰岛素的β细胞表达α干扰素。这些小鼠出现了低胰岛素血症性糖尿病，并伴有以胰岛为中心的混合性炎症。使用α干扰素的中和抗体可预防炎症和糖尿病。因此，β细胞表达α干扰素可能是1型糖尿病发病的原因，这提示了一种针对该疾病的治疗方法。
