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TCF 1 deficiency ameliorates autoimmune lymphoproliferative syndrome ( ALPS )‐like phenotypes of lpr/lpr mice
Author(s) -
Xu X.,
Yu B.,
Cai W.,
Huang Z.
Publication year - 2017
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12546
Subject(s) - autoimmune lymphoproliferative syndrome , phenotype , immunology , lymphoproliferative disorders , medicine , biology , genetics , gene , lymphoma , apoptosis , fas receptor , programmed cell death
Abstract Autoimmune lymphoproliferative syndrome ( ALPS ) is an incurable disease, which is characterized by non‐malignant autoimmune lymphoproliferation. TCF 1 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 TCF 1 in the development of ALPS ‐like phenotypes of lpr/lpr mice. We acquired TCF 1 −/− lpr/lpr double mutant mice by crossing TCF 1 deficiency mice with lpr/lpr mice. Splenocyte compositions, serum cytokines levels, antids DNA antibody production and kidney pathology were examined in the TCF 1 −/− lpr/lpr mice. With these examinations, we revealed that TCF 1 deficiency relieved most manifestations of ALPS ‐like phenotype, which were caused by Fas mutation in TCF 1 −/− 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 TCF 1 −/− 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 TCF 1 −/− lpr/lpr mice. Our study demonstrated that TCF 1 deficiency ameliorated the ALPS ‐like phenotypes of TCF 1 −/− lpr/lpr mice, which might indicate a potential therapeutic direction for ALPS .