The translocator protein (TSPO) ligands affected inflammatory and immune responses. However, the exact effects of TSPO ligands on Th1 responses in vitro and in vivo are still unclear. In the present study, we found that TSPO ligands, FGIN1-27 and Ro5-4864, suppressed the cytokine production in a dose-dependent manner by purified human CD4+ T-cells from peripheral blood mononuclear cells (PBMCs) after stimulation. TSPO ligands inhibited the production of interferon γ (IFN-γ) by memory CD4+ T-cells and the differentiation of naïve CD4+ T-cells into Th1 cells via suppressing the activity of the corresponding transcription factors as indicated by reduced expression of T-bet and down-regulation of STAT1, STAT4 and STAT5 phosphorylation. TSPO ligands suppressed cell proliferation and activation of CD4+ T-cells by the inhibition of TCR signal transduction including membrane proteins: Zap, Lck, Src; cytoplasm proteins: Plcγ1, Slp-76, ERK, JNK and the nucleoproteins: c-Jun and c-Fos. In addition, FGIN1-27 inhibited mixed lymphocyte reactions by human or murine cells. After the transplantation of allogeneic murine skin, injection of FGIN1-27 into mice prevented graft rejection by inhibition of cell infiltration and IFN-γ production. Taken together, our data suggest that TSPO ligands inhibit Th1 cell responses and might be novel therapeutic medicine for the treatment of autoimmune diseases and prevention of transplant rejection.
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Density-dependent scanning electron microscopy of calcifying vascular tissue (orange - calcification; green - collagen). Please see pp. 181-195 for more information. Image provided by Sergio Bertazzo.Close Modal
Research Article|
January 30 2017
The ligands of translocator protein inhibit human Th1 responses and the rejection of murine skin allografts
Yannan Zhang;
Yannan Zhang
*Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology; Institute of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China
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Sifei Yu;
Sifei Yu
*Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology; Institute of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China
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Xiaomin Li;
Xiaomin Li
*Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology; Institute of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China
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Binyan Yang;
Binyan Yang
*Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology; Institute of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China
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Changyou Wu
*Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology; Institute of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China
Correspondence: Changyou Wu (email changyou_wu@yahoo.com).
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Clin Sci (Lond) (2017) 131 (4): 297–308.
Article history
Received:
July 19 2016
Revision Received:
November 27 2016
Accepted:
December 06 2016
Accepted Manuscript online:
December 06 2016
Citation
Yannan Zhang, Sifei Yu, Xiaomin Li, Binyan Yang, Changyou Wu; The ligands of translocator protein inhibit human Th1 responses and the rejection of murine skin allografts. Clin Sci (Lond) 1 February 2017; 131 (4): 297–308. doi: https://doi.org/10.1042/CS20160547
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