Department of Neurology, University of California, Irvine, USA.
Ann N Y Acad Sci. 2012 Apr;1253:49-57. doi: 10.1111/j.1749-6632.2011.06391.x. Epub 2012 Jan 30.
T cell activation and self-tolerance are tightly regulated to provide effective host defense against foreign pathogens while deflecting inappropriate autoimmune responses. Golgi Asn (N)-linked protein glycosylation coregulates homeostatic set points for T cell growth, differentiation, and self-tolerance to influence risk of autoimmune disorders such as multiple sclerosis (MS). Human autoimmunity is a complex trait that develops from intricate and poorly understood interactions between an individual's genetics and their environmental exposures. Recent evidence from our group suggests that in MS, additive and/or epistatic interactions between multiple genetic and environmental risk factors combine to dysregulate a common biochemical pathway, namely Golgi N-glycosylation. Here, we review the multiple regulatory mechanisms controlling N-glycan branching in T cells and autoimmunity, focusing on recent data implicating a critical role for interleukin-2 (IL-2) and IL-7 signaling.
T 细胞的激活和自身耐受受到严格调控，以提供有效防御外来病原体的能力，同时避免不适当的自身免疫反应。高尔基体天冬酰胺（N）-连接蛋白糖基化共同调节 T 细胞生长、分化和自身耐受的稳态设定点，从而影响多发性硬化症（MS）等自身免疫性疾病的风险。人类自身免疫是一种复杂的特征，它是由个体的遗传因素和环境暴露之间复杂且尚未完全理解的相互作用而发展起来的。我们小组的最近证据表明，在多发性硬化症中，多个遗传和环境风险因素之间的累加和/或上位性相互作用结合起来，使一个共同的生化途径（即高尔基体 N-糖基化）失调。在这里，我们综述了控制 T 细胞和自身免疫中 N-聚糖分支的多种调控机制，重点关注最近的数据表明白细胞介素 2（IL-2）和白细胞介素 7（IL-7）信号的关键作用。
