Radical innate regulation of autoimmune diabetes.
Radical innate regulation of autoimmune diabetes.
复制标题
自身免疫性糖尿病的根本先天调节。
DOI：
10.1016/j.freeradbiomed.2012.02.024
复制
发表时间：
2012
影响因子：
7.4
通讯作者：
Kevil,ChristopherG
中科院分区：
文献类型：
--
作者：
Ostanin,DmitryV;Kevil,ChristopherG
Generation of reactive oxygen and nitrogen species (ROS/RNS) during various immune responses are critically important for innate defenses such as acute inflammation by neutrophils and macrophages for efficient killing of foreign pathogens. On the other hand, accumulation of ROS-producing cells during chronic inflammation often results in tissue damage. It is also becoming increasingly apparent that oxidative stress plays a significant role in the pathogenesis of a number of autoimmune diseases [1].Oxidative stress is well characterized by an imbalance of either endogenous cellular antioxidant defenses or generation of reactive oxygen and nitrogen species, both of which are locked in a reciprocal cycle of regulatory control. At the same time, it has been difficult to differentiate the cause and the effect relationship of ROS and its role in the pathogenesis of autoimmunity, as chronic inflammation inevitably leads to accumulation of immune cells responsible for oxidant production and subsequent redox imbalance. Nevertheless some organs and associated diseases may be intrinsically more susceptible to redox stress, which may initiate deterioration of tissue function and facilitate progression of autoimmunity, as seen during Type 1 diabetes. Type 1 diabetes (T1D) is a metabolic disease characterized by the inability to produce insulin in response to elevated blood glucose due to autoimmune destruction of pancreatic beta cells that are responsible for production of insulin. Because of the naturally low anti-oxidant defenses in beta cells [2], chronic hyperglycemia has also been linked to ROS production within these cells leading to redox imbalance and beta cell apoptosis which may also be observed during Type 2 diabetes [3]. However, the causative role of oxidative stress in T1D is less well understood. It is thought that genetic and/or environmental factors may lead to initial dysfunction of beta cells involving necrosis and uptake of damaged beta cells by tissue macrophages and their subsequent migration to the pancreatic lymph nodes where generation of auto-reactive T and B cells further amplify the disease process. Likewise, inherent immune cell dysfunction involving T and B cell development and activation also play key roles during autoimmune diabetes pathogenesis. Together, the recruitment of circulating immune cells, including mononuclear myeloid cell populations produce a variety of pro-inflammatory cytokines and ROS that cooperatively exacerbate the development of Type 1 diabetes.
