TCF1 deficiency ameliorates autoimmune lymphoproliferative syndrome (ALPS)-like phenotypes of lpr/lpr mice

Autoimmune lymphoproliferative syndrome (ALPS) is an incurable disease, which is characterized by non-malignant autoimmune lymphoproliferation. TCF1 is a key effector in the canonical Wnt/β-catenin pathway, regulating the development, activation and function of T cells. In this study, we aimed to explore the potential role of TCF1 in the development of ALPS-like phenotypes of lpr/lpr mice. We acquired TCF1^-/- lpr/lpr double mutant mice by crossing TCF1 deficiency mice with lpr/lpr mice. Splenocyte compositions, serum cytokines levels, antidsDNA antibody production and kidney pathology were examined in the TCF1^-/- lpr/lpr mice. With these examinations, we revealed that TCF1 deficiency relieved most manifestations of ALPS-like phenotype, which were caused by Fas mutation in TCF1^-/- lpr/lpr mice. Splenocyte total numbers and compositions were downregulated to the similar levels with wildtype mice. T_E and T_EM cells were decreased in TCF1^-/- lpr/lpr compared with lpr/lpr mice. The levels of autoantibodies and proinflammatory factors in serum, and the histopathology changes and the relative mRNA levels of proinflammatory factors in kidney all displayed parallel tendency in TCF1^-/- lpr/lpr mice. Our study demonstrated that TCF1 deficiency ameliorated the ALPS-like phenotypes of TCF1^-/- lpr/lpr mice, which might indicate a potential therapeutic direction for ALPS.