Role of CD200/CD200R Signaling Pathway in Regulation of CD4+T Cell Subsets During Thermal Ablation of Hepatocellular Carcinoma

Med Sci Monit. 2019 Mar 6:25:1718-1728. doi: 10.12659/MSM.913094.

Abstract

BACKGROUND In this study, we assessed the role of CD200 and CD200 receptor (CD200R) in regulating CD4+T cell subsets and assessed the therapeutic efficacy of thermal ablation for liver hepatocellular carcinoma (HCC) in rats. MATERIAL AND METHODS Seventy-eight male C57BL/6 rats were randomly divided into 7 groups: a control group, a model group, a CD200FC group, an anti-CD200R1 mAb group, a thermal ablation group, a thermal ablation+CD200 FC group, and a thermal ablation+anti-CD200R1 mAb group. The levels of CD200, CD200R1, Th1, Th17, and Treg in peripheral blood were detected by flow cytometry. Immunohistochemistry was used to detect CD200, CD200R1, IFN-γ, IL-17, Foxp3 protein expression in tumor tissues. RESULTS The levels of CD200, CD200R1, Th17, and Treg were significantly increased after CD200FC treatment (p<0.05). After treatment with anti-CD200R1 mAb, the levels of CD200, CD200R1, Th17, and Treg decreased and Th1 increased. Compared with the control group, the expression of CD200, CD200R1, IL-17, and Foxp3 in the model group increased significantly, and the expression of IFN-γ decreased significantly (p<0.05). The expression of CD200, CD200R1, IL-17, and Foxp3 was significantly reduced by adding anti-CD200R1 mAb, and the expression of IFN-γ was increased (p<0.05). After the thermal ablation treatment, the proteins continued to decrease and the expression of IFN-γ continued to increase. CONCLUSIONS The CD200/CD200R pathway participates in HCC tumor growth and the expression of CD4+T cell subsets in cancer tissues. Furthermore, thermal ablation treatment inhibited cancer recurrence.

MeSH terms

  • Ablation Techniques / methods*
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / physiology
  • Antigens, Surface / metabolism
  • CD4-Positive T-Lymphocytes / physiology
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / physiopathology
  • China
  • Flow Cytometry
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / physiopathology
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Recurrence, Local
  • Receptors, Cell Surface / metabolism
  • Signal Transduction / physiology
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / metabolism

Substances

  • Antigens, CD
  • Antigens, Surface
  • CD200 receptor, mouse
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • antigens, CD200