Stabilized [beta]-Catenin Ameliorates ALPS-Like Symptoms of B6/lpr Mice

Autoimmune lymphoproliferative syndrome (ALPS) is an incurable disease mainly caused by the defect of Fas-mediated apoptosis and characterized by nonmalignant autoimmune lymphoproliferation. Stabilized [beta]-catenin could not only potentiate Fasmediated T cell apoptosis via upregulating the expression of Fas on activated T cells, but also potentiate T cell apoptosis via intrinsic apoptotic pathway. In the present study, we introduced [beta]-[cat.sup.Tg] into lpr/lpr mice and aimed to explore the potential role of stabilized [beta]-catenin ([beta]-[cat.sup.Tg]) in the development of ALPS-like phenotypes of lpr/lpr mice. We found that the total splenocyte cells and some compositions were slightly downregulated in [beta]-[cat.sup.Tg]lpr/lpr mice, especially the CD4 and CD8 [T.sub.EM] cells were significantly reduced. Meanwhile, stabilized [beta]-catenin obviously decreased the numbers of spleen TCR[[beta].sup.+] [CD4.sup.-][CD8.sup.-] T (DNT) cells, and the levels of some serum proinflammatory factors also were lowered in [beta]- [cat.sup.Tg]lpr/lpr mice. Beyond that, stabilized [beta]-catenin slightly lowered the levels of the serum autoantibodies and the scores of kidney histopathology of [beta]-[cat.sup.Tg]lpr/lpr mice compared with lpr/lpr mice. Our study suggested that stabilized [beta]- catenin ameliorated some ALPS-like symptoms of lpr/lpr mice by potentiating Fas-independent signal-mediated T cell apoptosis, which might uncover a potential novel therapeutic direction for ALPS.