Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL-/- mice.
TRAIL, the tumor necrosis factor-related apoptosis-inducing ligand, selectively induces apoptosis of tumor cells, but not most normal cells. Its role in normal, nontransformed tissues is not clear. We report here that mice deficient in TRAIL have a severe defect in thymocyte apoptosis-thus, thymic deletion induced by T cell receptor ligation is severely impaired. TRAIL-deficient mice are also hypersensitive to collagen-induced arthritis and streptozotocin-induced diabetes and develop heightened autoimmune responses. Thus, TRAIL mediates thymocyte apoptosis and is important in the induction of autoimmune diseases.
Lamhamedi-Cherradi
Salah-Eddine
SE
Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zheng
Shi-Jun
SJ
Maguschak
Kimberly A
KA
Peschon
Jacques
J
Chen
Youhai H
YH
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D017637:Clonal Deletion / Q000276:immunology; D003094:Collagen / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin; D003094:Collagen