Bai-Sui Feng1, Na Ma1, Yuan-Yi Zhang2, Han Gao3, Cui Zhang3, Gengfeng Li3, Zhanju Liu3, Yisheng Feng4, Hai-Qiong Yu5, Liang Xiao6, Zhi-Gang Liu2, Ping-Chang Yang7. 1. Department of Gastroenterology, Second Hospital, Zhengzhou University, Zhengzhou, China. 2. Research Center of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, China. 3. Department of Gastroenterology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China. 4. Department of Colorectal Surgery, Kunshan Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Kunshan City, China. 5. Department of Respirology, Third Affiliated Hospital of Shenzhen University, Shenzhen, China. 6. Metagenomic Institute, BGI Research GeneBank, Shenzhen, China. 7. Research Center of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, China, pcy2356@163.com.
Abstract
BACKGROUND: The increase in CD4+ T cell infiltration and overproduction of CD4+ T cell-associated cytokines have been observed in the inflamed colon mucosa of patients with ulcerative colitis (UC); the underlying mechanisms are not fully understood. Survivin plays a critical role in the interference with apoptotic machinery. This study aims to elucidate the role of survivin in the interference with the apoptotic machinery in CD4+ T cells of UC patients. METHODS: Peripheral blood samples were collected from UC patients (UC group) and healthy subjects (healthy group). The apoptotic status in CD4+ T cells was analyzed by flow cytometry. RESULTS: We observed that the expression of survivin was significantly higher in CD4+ T cells of UC patients than in healthy subjects. UC CD4+ T cells were resistant to apoptosis induction. A complex of survivin and c-Myc, the transcription factor of FasL, was detected in CD4+ T cells in UC patients, which prevented the binding of c-Myc to the FasL promoter and interfered with the expression of FasL. Increased expression of survivin prevented the activation-induced CD4+ T cells from apoptosis. CONCLUSIONS: The data indicate that UC CD4+ T cells express high levels of survivin, which impairs the apoptotic machinery in CD4+ T cells and prevents the activation-induced CD4+ T cell apoptosis. Therefore, target therapy against survivin has translational potential in the treatment of UC patients.
BACKGROUND: The increase in CD4+ T cell infiltration and overproduction of CD4+ T cell-associated cytokines have been observed in the inflamed colon mucosa of patients with ulcerative colitis (UC); the underlying mechanisms are not fully understood. Survivin plays a critical role in the interference with apoptotic machinery. This study aims to elucidate the role of survivin in the interference with the apoptotic machinery in CD4+ T cells of UC patients. METHODS: Peripheral blood samples were collected from UC patients (UC group) and healthy subjects (healthy group). The apoptotic status in CD4+ T cells was analyzed by flow cytometry. RESULTS: We observed that the expression of survivin was significantly higher in CD4+ T cells of UC patients than in healthy subjects. UC CD4+ T cells were resistant to apoptosis induction. A complex of survivin and c-Myc, the transcription factor of FasL, was detected in CD4+ T cells in UC patients, which prevented the binding of c-Myc to the FasL promoter and interfered with the expression of FasL. Increased expression of survivin prevented the activation-induced CD4+ T cells from apoptosis. CONCLUSIONS: The data indicate that UC CD4+ T cells express high levels of survivin, which impairs the apoptotic machinery in CD4+ T cells and prevents the activation-induced CD4+ T cell apoptosis. Therefore, target therapy against survivin has translational potential in the treatment of UC patients.
Authors: G Gravina; C Wasén; M J Garcia-Bonete; M Turkkila; M C Erlandsson; S Töyrä Silfverswärd; M Brisslert; R Pullerits; K M Andersson; G Katona; M I Bokarewa Journal: Autoimmun Rev Date: 2017-05-28 Impact factor: 9.754
Authors: Ivan J Fuss; Frank Heller; Monica Boirivant; Francisco Leon; Masaru Yoshida; Stefan Fichtner-Feigl; Zhiqiong Yang; Mark Exley; Atsushi Kitani; Richard S Blumberg; Peter Mannon; Warren Strober Journal: J Clin Invest Date: 2004-05 Impact factor: 14.808