title: Role of endogenous 4-1BB in the development of systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is characterized by the production of autoantibodies directed against nuclear antigens including nucleosomes and DNA. To determine the role of T-cell costimulatory molecule 4-1BB in the regulation of SLE, MRL-Fas(lpr) (lpr) mice deficient in 4-1BB (lpr/4-1BB(-/-)) were generated and their disease phenotype was compared to that of control lpr mice. The main finding of this study is that the lpr/4-1BB(-/-) mice had more pronounced skin lesions which appeared earlier, increased lymphadenopathy, increased renal damage, and higher mortality than 4-1BB-intact control lpr mice. The increased severity of lesions in lpr/4-1BB(-/-) mice was closely associated with increases in CD4(+) T, CD3(+) B220(+) double-negative T cells, serum immunoglobulin, anti-dsDNA autoantibodies, and tissue immunoglobulin deposits. These data suggest that the 4-1BB-4-1BB ligand signalling pathway plays an important role in SLE and that deletion of 4-1BB confers susceptibility to lpr mice, leading to accelerated induction of disease and early mortality.
authors.affiliation: LSU Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans, LA, USA.
authors.forename: Dass S
authors.initials: DS
authors.lastname: Vinay
authors.forename: Jae H
authors.initials: JH
authors.lastname: Choi
authors.forename: Jung D
authors.initials: JD
authors.lastname: Kim
authors.forename: Beom K
authors.initials: BK
authors.lastname: Choi
authors.forename: Byoung S
authors.initials: BS
authors.lastname: Kwon
mesh_terms: D000208:Acute Disease; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology; D008206:Lymphatic Diseases / Q000276:immunology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D012871:Skin Diseases / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology; D013163:Splenomegaly / Q000276:immunology; D016019:Survival Analysis; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000172:deficiency / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9