Case Report: IL-21 and Bcl-6 Regulate the Proliferation and Secretion of Tfh and Tfr Cells in the Intestinal Germinal Center of Patients With Inflammatory Bowel Disease.

Objective: This study aimed to investigate the effect of interleukin (IL)-21 and B cell lymphoma protein-6 on germinal center follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells and its relationship with the clinical features of inflammatory bowel disease (IBD). Methods: The expression of peripheral blood cytokines IL-21 and Bcl-6 mRNA was detected by reverse transcription-polymerase chain reaction. The distribution characteristics of Tfh and Tfr cells were detected using the triple immunofluorescence staining analysis. Results: The expression of IL-21 and Bcl-6 mRNA was upregulated in the ulcerative colitis (UC) and Crohn disease (CD) groups compared with that in the control group. Triple immunofluorescence staining showed that the number of Tfh cells in the intestinal germinal center obviously increased in the UC and CD groups compared with that in the control group, whereas the number of Tfr cells reduced. Conclusion: This study suggested that the Tfr and Tfh cells might be involved in the regulation of IBD. Bcl-6 and IL-21 can regulate the Tfh/Tfr ratio in the intestinal germinal center, promoting the occurrence and development of IBD.

Human urokinase-type plasminogen activator gene-modified bone marrow-derived mesenchymal stem cells attenuate liver fibrosis in rats by down-regulating the Wnt signaling pathway.

AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells (BMSCs) with human urokinase-type plasminogen activator (uPA) on liver fibrosis, and to investigate the mechanism of gene therapy. METHODS: BMSCs transfected with adenovirus-mediated human urokinase plasminogen activator (Ad-uPA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and mRNA expression levels. RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type III were markedly decreased, whereas the levels of serum albumin were increased by uPA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while uPA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area (16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment (12.38% ± 2.27%) and was further reduced by uPA-BMSCs treatment (8.31% ± 1.21%). Both protein and mRNA expression of ß-catenin, Wnt4 and Wnt5a was down-regulated in liver tissues following uPA gene modified BMSCs treatment when compared with the model animals. CONCLUSION: Transplantation of uPA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with uPA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway.