Dataset Information

Survivin Impairs the Apoptotic Machinery in CD4+ T Cells of Patients with Ulcerative Colitis.

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.

SUBMITTER: Feng BS

PROVIDER: S-EPMC7265744 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Survivin Impairs the Apoptotic Machinery in CD4+ T Cells of Patients with Ulcerative Colitis.

Feng Bai-Sui BS Ma Na N Zhang Yuan-Yi YY Gao Han H Zhang Cui C Li Gengfeng G Liu Zhanju Z Feng Yisheng Y Yu Hai-Qiong HQ Xiao Liang L Liu Zhi-Gang ZG Yang Ping-Chang PC

Journal of innate immunity 20190722 3

<h4>Background</h4>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.<h4>Methods</h4>Peripheral blood sam ...[more]

PMID: 31330513

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Project description:BackgroundPrevious studies have indicated that the appendix may be a priming site of ulcerative colitis (UC). Appendectomy is inversely associated with the development of UC, and is suggested to have a beneficial effect on the disease course in patients with refractory disease.ObjectiveThe aim of the current study was to assess histological features of appendices from patients with UC and their clinical relevance.MethodsPatients with UC in remission and active UC (therapy refractory) that underwent appendectomy between 2012 and 2019 were included. Histological features of UC appendices were compared to those of patients with acute appendicitis and colon carcinoma. The Robarts Histopathology Index (RHI) was used to assess appendiceal inflammation. In patients with active UC, histological and clinical characteristics were compared between patients with and without endoscopic response following appendectomy.ResultsIn total, 140 appendix specimens were assessed (n = 35 UC remission, n = 35 active UC, n = 35 acute appendicitis, n = 35 colon carcinoma). Histological features of appendices from UC patients looked like UC rather than acute appendicitis. The presence of active appendiceal inflammation was comparable between patients in remission versus active disease (53.7% vs. 46.3%, p = 0.45) and limited versus extensive disease (58.5% vs. 41.5%, p = 0.50). Endoscopic response (Mayo 0-1) following appendectomy, assessed in 28 therapy refractory patients, was more frequently seen in patients with higher RHI scores (RHI > 6: 81.8% vs. RHI ≤ 6: 9.1%, p = 0.03) and limited disease (proctitis/left sided 63.6% vs. pancolitis 36.4%, p = 0.02).ConclusionThe presence of active appendiceal inflammation is common in UC and does not correlate with colonic disease activity. More than 50% of UC patients in remission showed active histological disease in the appendix. Favorable response to appendectomy for refractory UC was seen in cases with ulcerative appendicitis. These findings might support the role of the appendix as a pivotal organ in UC.

Dataset Information

Survivin Impairs the Apoptotic Machinery in CD4+ T Cells of Patients with Ulcerative Colitis.

Background

Methods

Results

Conclusions

Publications

Survivin Impairs the Apoptotic Machinery in CD4+ T Cells of Patients with Ulcerative Colitis.

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