TNF, apoptosis and autoimmunity: a common thread?
A subset of cytokine mediators belonging to the tumor necrosis factor (TNF) family cause apoptosis, acting through receptors and signaling pathways that have recently come to light. Further, at least one autoimmune disease results from a defined defect of apoptosis (mutations of the Fas ligand or its receptor). It is offered that many, and perhaps most autoimmune diseases may result from primary defects of apoptosis. Such defects may cause reflexive overproduction of TNF and other pro-apoptotic cytokines. The collateral damage produced by these mediators may be of pathogenetic importance in complex autoimmune disorders such as rheumatoid arthritis and Crohn disease, wherein TNF blockade is known to have ameliorative effects.
Beutler
B
B
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas 75235-9050, USA. beutler@howie.swmed.edu
Bazzoni
F
F
D017209:Apoptosis / Q000502:physiology*; D001327:Autoimmune Diseases / Q000235:genetics; D015551:Autoimmunity / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D019281:Dimerization; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation; D008562:Membrane Glycoproteins / Q000502:physiology; D018448:Models, Immunological; D005810:Multigene Family; D010641:Phenotype; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D016335:Zinc Fingers / Q000502:physiology
D004268:DNA-Binding Proteins; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha