title: Cell-penetrable mouse forkhead box protein 3 alleviates experimental arthritis in mice by up-regulating regulatory T cells.
abstract: Regulatory T cells (T(regs)) have potential applications in clinical disease therapy, such as autoimmune diseases and transplant rejection. However, their numbers are limited. Forkhead box protein 3 (FoxP3) is a key transcription factor that controls T(reg) development and function. Here, we generated a cell-permeable fusion protein, protein transduction domain (PTD)-conjugated mouse FoxP3 protein (PTD-mFoxP3), and evaluated whether PTD-mFoxp3 can alleviate rheumatoid arthritis (RA) in the collagen-induced arthritis (CIA) mouse model. As expected, PTD-mFoxP3 was transduced into cells effectively, and inhibited T cell activation and attenuated the cell proliferation. It decreased interleukin (IL) 2 and interferon (IFN)-γ expression, and increased IL-10 expression in activated CD4(+)CD25(-) T cells. PTD-mFoxP3-transduced CD4(+)CD25(-) T cells attenuated proliferation of activated CD4(+)CD25(-) T cells. In addition, PTD-mFoxP3 blocked the Th17 differentiation programme in vitro and down-regulated IL-17 production from T cells by modulating induction and levels of retinoid-related orphan receptor gamma t (RORγt). Intra-articular delivery of PTD-mFoxP3 delayed disease incidence remarkably and alleviated autoimmune symptoms of CIA mice. Moreover, protective effects of PTD-mFoxP3 were associated with regulating the balance of T helper type 17 (Th17) and T(regs). These results suggest that PTD-mFoxP3 may be a candidate for RA therapy.
authors: Department of Immunology, and Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu.
authors: Xia
authors: X
authors: Liu
authors: Department of Immunology, and Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu.|Department of Clinical Laboratory, Linyi People's Hospital, Linyi.
authors: Baoju
authors: B
authors: Ji
authors: Department of Immunology, and Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu.|Department of Clinical Laboratory, Shandong Jining No.1 People's Hospital, Shandong.
authors: Mengyi
authors: M
authors: Sun
authors: Department of Immunology, and Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu.
authors: Weijiang
authors: W
authors: Wu
authors: Department of Immunology, and Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu.
authors: Lili
authors: L
authors: Huang
authors: Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu.
authors: Aihua
authors: A
authors: Sun
authors: Department of Immunology, and Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu.
authors: Yangyong
authors: Y
authors: Zong
authors: Department of Immunology, and Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu.
authors: Sheng
authors: S
authors: Xia
authors: Department of Basic Medical Science, Key Laboratory of Inflammation and Immunoregulation, School of Medicine, Hangzhou Normal University, Zhejiang, China.
authors: Liyun
authors: L
authors: Shi
authors: Department of Immunology, and Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu.
authors: Hui
authors: H
authors: Qian
authors: Department of Immunology, and Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu.
authors: Wenrong
authors: W
authors: Xu
authors: Department of Immunology, and Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu.
authors: Qixiang
authors: Q
authors: Shao
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology; D015854:Up-Regulation
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; C508018:Il2ra protein, mouse; D020381:Interleukin-17; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: FoxP3; PTD; Tregs; collagen-induced arthritis; rheumatoid arthritis