Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, 410011, Hunan, China.
J Mol Med (Berl). 2018 Aug;96(8):741-751. doi: 10.1007/s00109-018-1660-7. Epub 2018 Jul 12.
The immune system can be divided into adaptive immunity and innate immunity. Adaptive immunity has been confirmed to be involved in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D). However, the role of innate immunity in T1D has only been studied recently. T1D is caused by selective autoimmune destruction of pancreatic islet β cells. A series of studies have suggested that TLRs play a critical role in the pathogenesis of T1D. Aberrant TLR signaling will change immune homeostasis and result in immunopathological conditions such as endotoxin shock and autoimmune responses. Thus, TLR signaling pathways are supposed to be strictly and finely regulated. Epigenetics has recently been proven to be a new regulator of TLR expression. DNA methylation, histone modification, and microRNAs are the three main epigenetic modifications. This review will mainly focus on these epigenetic mechanisms of regulation of TLRs and the role of TLRs in the pathogenesis of T1D.
免疫系统可分为适应性免疫和固有免疫。适应性免疫已被证实与自身免疫性疾病的发病机制有关，包括 1 型糖尿病（T1D）。然而，固有免疫在 T1D 中的作用直到最近才被研究。T1D 是由胰腺胰岛β细胞的选择性自身免疫破坏引起的。一系列研究表明，TLRs 在 T1D 的发病机制中起关键作用。TLR 信号异常会改变免疫稳态，导致内毒素休克和自身免疫反应等免疫病理状况。因此，TLR 信号通路应该受到严格和精细的调节。最近已经证明表观遗传学是 TLR 表达的一个新的调节剂。DNA 甲基化、组蛋白修饰和 microRNAs 是三种主要的表观遗传修饰。这篇综述将主要集中在 TLRs 的这些表观遗传调节机制以及 TLRs 在 T1D 发病机制中的作用。
