Fas Stefanie C, Fritzsching Benedikt, Suri-Payer Elisabeth, Krammer Peter H
Tumor Immunology Program, Division of Immunogenetics, German Cancer Research Center, Heidelberg, Germany.
Curr Dir Autoimmun. 2006;9:1-17. doi: 10.1159/000090767.
Death receptors belong to the TNF (tumor necrosis factor)/NGF (nerve growth factor) receptor superfamily. Signaling via death receptors plays a distinct role, e.g. in the immune system, where it contributes to regulation of the adaptive immune response in various ways, most notably by triggering activation-induced cell death (AICD) of T cells. Thus, dysregulation of death receptor signaling, either allowing too much or too little apoptosis, can lead to autoimmune disorders and also impacts on tumorigenesis or other diseases. In this chapter we address components, molecular mechanisms and regulation of death receptor signaling with particular focus on CD95 (APO-1, Fas). We discuss the role of death receptor-mediated AICD in regulation of the adaptive immune response against foreign and self antigens in comparison to cytokine deprivation-mediated death by neglect. Finally, the contribution of dysregulated death receptor/ligand systems to autoimmune diseases such as diabetes, multiple sclerosis and Hashimoto's thyroiditis is discussed.
死亡受体属于肿瘤坏死因子（TNF）/神经生长因子（NGF）受体超家族。通过死亡受体进行的信号传导发挥着独特作用，例如在免疫系统中，它以多种方式参与适应性免疫反应的调节，最显著的是通过触发T细胞的活化诱导细胞死亡（AICD）。因此，死亡受体信号传导失调，无论是导致过多还是过少的细胞凋亡，都可能引发自身免疫性疾病，也会影响肿瘤发生或其他疾病。在本章中，我们将探讨死亡受体信号传导的组成部分、分子机制和调节，特别关注CD95（APO-1，Fas）。我们将比较死亡受体介导的AICD与因忽视细胞因子剥夺介导的死亡在针对外来和自身抗原的适应性免疫反应调节中的作用。最后，将讨论死亡受体/配体系统失调对糖尿病、多发性硬化症和桥本甲状腺炎等自身免疫性疾病的影响。
