Death receptor signaling and its function in the immune system.
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.
Fas
Stefanie C
SC
Tumor Immunology Program, Division of Immunogenetics, German Cancer Research Center, Heidelberg, Germany.
Fritzsching
Benedikt
B
Suri-Payer
Elisabeth
E
Krammer
Peter H
PH
D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D006801:Humans; D007107:Immune System / Q000502:physiology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D053219:Receptors, Tumor Necrosis Factor, Member 25; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; D047888:Receptors, Tumor Necrosis Factor, Type I; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C114109:TNFRSF21 protein, human; C506033:TNFRSF25 protein, human; D019014:fas Receptor