Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO 80045, USA.
Adv Exp Med Biol. 2010;654:585-610. doi: 10.1007/978-90-481-3271-3_25.
Type 1 diabetes (T1D) is an autoimmune disease that results in the progressive loss of insulin producing cells. Studies performed in humans with T1D and animal models of the disease over the past two decades have suggested a key role for the adaptive immune system in disease mechanisms. The role of the innate immune system in triggering T1D was shown only recently. Research in this area was greatly facilitated by the discovery of toll-like receptors (TLRs) that were found to be a key component of the innate immune system that detect microbial infections and initiate antimicrobial host defense responses. New data indicate that in some situations, the innate immune system is associated with mechanisms triggering autoimmune diabetes. In fact, studies preformed in the BioBreeding Diabetes Resistant (BBDR) and LEW1.WR1 rat models of T1D demonstrate that virus infection leads to islet destruction via mechanisms that may involve TLR9-induced innate immune system activation. Data from these studies also show that TLR upregulation can synergize with virus infection to dramatically increase disease penetrance. Reports from murine models of T1D implicate both MyD88-dependent and MyD88-independent pathways in the course of disease. The new knowledge about the role of innate immune pathways in triggering islet destruction could lead to the discovery of new molecules that may be targeted for disease prevention.
1 型糖尿病(T1D)是一种自身免疫性疾病,导致产生胰岛素的细胞逐渐丧失。在过去二十年中,对 T1D 患者和疾病动物模型进行的研究表明,适应性免疫系统在疾病机制中起关键作用。最近才显示出先天免疫系统在引发 T1D 中的作用。该领域的研究因发现 Toll 样受体(TLR)而得到极大促进,TLR 被发现是先天免疫系统的关键组成部分,可检测微生物感染并引发抗菌宿主防御反应。新数据表明,在某些情况下,先天免疫系统与引发自身免疫性糖尿病的机制有关。事实上,在 T1D 的 BioBreeding Diabetes Resistant(BBDR)和 LEW1.WR1 大鼠模型中进行的研究表明,病毒感染通过可能涉及 TLR9 诱导的先天免疫系统激活的机制导致胰岛破坏。这些研究的数据还表明,TLR 的上调可以与病毒感染协同作用,极大地增加疾病的通透性。来自 T1D 小鼠模型的报告表明,MyD88 依赖性和非依赖性途径都参与了疾病的进程。关于先天免疫途径在引发胰岛破坏中的作用的新知识可能会导致发现可针对疾病预防的新分子。