Interleukin 10 Gene-Modified Bone Marrow-Derived Dendritic Cells Attenuate Liver Fibrosis in Mice by Inducing Regulatory T Cells and Inhibiting the TGF-β /Smad Signaling Pathway

Mediators of Inflammation
Yejin XuMingqin Lu

Abstract

To explore the therapeutic effects and mechanisms of interleukin 10 gene-modified bone marrow-derived dendritic cells (DC-IL10) on liver fibrosis. In vitro, BMDCs were transfected with lentiviral-interleukin 10-GFP (LV-IL10-GFP) at the MOI of 1 : 40. Then, the phenotype (MHCII, CD80, and CD86) and allo-stimulatory ability of DC-IL10 were identified by flow cytometry, and the levels of IL-10 and IL-12 (p70) secreted into the culture supernatants were quantified by ELISA. In vivo, DC-IL10 was injected into mice with CCl4-induced liver fibrosis through the tail vein. Lymphocytes were isolated to investigate the differentiation of T cells, and serum and liver tissue were collected for biochemical, cytokine, histopathologic, immune-histochemical, and Western blot analyzes. In vitro, the expressions of MHCII, CD80, and CD86 in DC-IL10 were significantly suppressed, allogeneic CD4+T cells incubated with DC-IL10 showed a lower proliferative response, and the levels of IL-10 and IL-12 (p70) secreted into the DC-IL10 culture supernatants were significantly increased and decreased, respectively. In vivo, regulatory T cells (Tregs) were significantly increased, while ALT, AST, and inflammatory cytokines were significantly reduced in the DC...Continue Reading

References

Jun 1, 2004·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ming ZhangXuetao Cao
May 1, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yang-Gun SuhWon-Il Jeong
Mar 13, 2014·World Journal of Gastroenterology : WJG·Xiao-Fei SunQing Xu
Feb 9, 2017·Clinics and Research in Hepatology and Gastroenterology·Kun LiTao Guo
Apr 22, 2017·World Journal of Gastroenterology : WJG·Yi WangBei Zhang
Jun 5, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Zhiwei DongYizhi Peng
Jun 21, 2017·Journal of Leukocyte Biology·Georgina Flórez-GrauDaniel Benítez-Ribas
Jun 21, 2017·European Journal of Immunology·Klaus G Schmetterer, Winfried F Pickl
May 11, 2018·Oxidative Medicine and Cellular Longevity·Liteng LinKangshun Zhu

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Citations

May 10, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Julia KhantakovaSergey Sennikov
Nov 13, 2019·European Journal of Pharmacology·Liang-Yun LiTao Xu
Apr 3, 2020·Current Opinion in Biotechnology·Rita AhmedLana E Kandalaft
Oct 31, 2020·Frontiers in Immunology·Quan ZhuangYingzi Ming
May 12, 2021·Hepatobiliary & Pancreatic Diseases International : HBPD INT·Hao LiYing-Zi Ming
Jun 8, 2021·Frontiers in Immunology·Jinwen LinJianghua Chen

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Methods Mentioned

BETA
fluorescence microscopy
flow cytometry
ELISA
transfection
FACS
genetic

Software Mentioned

Quantity One 1 - D Analysis
FlowJo

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