Stabilized ?-Catenin Ameliorates ALPS-Like Symptoms of B6/lpr Mice.

ABSTRACT: Autoimmune lymphoproliferative syndrome (ALPS) is an incurable disease mainly caused by the defect of Fas-mediated apoptosis and characterized by nonmalignant autoimmune lymphoproliferation. Stabilized ?-catenin could not only potentiate Fas-mediated 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 ?-catTg into lpr/lpr mice and aimed to explore the potential role of stabilized ?-catenin (?-catTg) 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 ?-catTglpr/lpr mice, especially the CD4 and CD8 TEM cells were significantly reduced. Meanwhile, stabilized ?-catenin obviously decreased the numbers of spleen TCR?+CD4-CD8- T (DNT) cells, and the levels of some serum proinflammatory factors also were lowered in ?-catTglpr/lpr mice. Beyond that, stabilized ?-catenin slightly lowered the levels of the serum autoantibodies and the scores of kidney histopathology of ?-catTglpr/lpr mice compared with lpr/lpr mice. Our study suggested that stabilized ?-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.

SUBMITTER: Xu X 

PROVIDER: S-EPMC5700472 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature