tailieunhanh - Báo cáo y học: " FoxP3 and Bcl-xL cooperatively promote regulatory T cell persistence and prevention of arthritis development"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: FoxP3 and Bcl-xL cooperatively promote regulatory T cell persistence and prevention of arthritis development. | Haque et al. Arthritis Research Therapy 2010 12 R66 http content 12 2 R66 RESEARCH ARTICLE Open Access FoxP3 and Bcl-xL cooperatively promote regulatory T cell persistence and prevention of arthritis development Rizwanul Haque 1 Fengyang Lei1 Xiaofang Xiong1 Yuzhang Wu2 and Jianxun Song 1 2 Abstract Introduction Forkhead box p3 FoxP3 -expressing regulatory T cells Tregs have been clearly implicated in the control of autoimmune disease in murine models. In addition ectopic expression of FoxP3 conveys a Treg phenotype to CD4 T cells lending itself to therapeutic use in the prevention of rheumatoid arthritis RA . In this study we generated therapeutically active Tregs with an increased life span and hence greater therapeutic potential. Methods We used retrovirus-mediated transduction to introduce FoxP3 or FoxP3 with anti-apoptotic Bcl-2 family molecule Bcl-xL linked by a 2A picornavirus self-cleaving peptide into CD4 T cells to generate Tregs. In addition by using in vitro functional analyses and adoptive immunotherapy in a murine model of RA we demonstrated that these Tregs were highly reactive. Results We found that CD4 T cells expressing both FoxP3 and Bcl-xL were able to differentiate into functional Tregs which have a long-term survival advantage over cells transduced with FoxP3 alone. In an in vivo murine model adoptive transfer of Tregs expressing both FoxP3 and Bcl-xL demonstrated more effective suppression of RA than CD4 T cells expressing FoxP3 alone. Conclusions FoxP3 and Bcl-xL can cooperatively promote the differentiation and persistence of Tregs with the capacity to prevent arthritis. Our results provide a novel approach for generating highly reactive Tregs for augmenting cellular immunotherapy for autoimmune disease. Introduction Regulatory T cells Tregs are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens. .