Role of endogenous 4‐1BB in the development of systemic lupus erythematosus
Open Access
- 29 June 2007
- journal article
- Published by Wiley in Immunology
- Vol. 122 (3), 394-400
- https://doi.org/10.1111/j.1365-2567.2007.02653.x
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-Faslpr (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.Keywords
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