Defective T cell activation and autoimmune disorder in Stra13-deficient mice.
Stra13, a basic helix-loop-helix transcription factor, is up-regulated upon activation of CD4+ T cells. Here we show that Stra13-deficient mice exhibit defects in several phases of CD4+ T cell activation. In vivo, Stra13 deficiency results in ineffective elimination of activated T and B cells, which accumulate progressively, leading to lymphoid organ hyperplasia. Consequently, aging Stra13-/- mice develop autoimmune disease characterized by accumulation of spontaneously activated T and B cells, circulating autoantibodies, infiltration of T and B lymphocytes in several organs and immune complex deposition in glomeruli. Our studies identify Stra13 as a key regulator of lymphocyte activation that is vital for maintenance of self-tolerance and for constraint of autoimmunity.
Sun
H
H
Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Lu
B
B
Li
R Q
RQ
Flavell
R A
RA
Taneja
R
R
D000375:Aging / Q000276:immunology; D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D002678:Chimera; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D053222:Fas Ligand Protein; D005260:Female; D005786:Gene Expression Regulation; D018390:Gene Targeting; D005838:Genotype; D005921:Glomerulonephritis / Q000209:etiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006965:Hyperplasia; D007105:Immune Complex Diseases / Q000209:etiology; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000502:physiology*; D008221:Lymphoid Tissue / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000473:pathology; D019014:fas Receptor / Q000502:physiology
D001323:Autoantibodies; D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D053222:Fas Ligand Protein; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D019014:fas Receptor; C491539:Bhlhe40 protein, mouse; C505658:Fasl protein, mouse