IL-6 induced proliferation and cytotoxic activity of CD8(+) T cells is elevated by SUMO2 overexpression

Arch Pharm Res. 2016 May;39(5):705-12. doi: 10.1007/s12272-016-0736-6. Epub 2016 Apr 12.

Abstract

T cells play an important role in adaptive immune responses that destroy pathogens or infected cells. Therefore, regulation of T cell activity is important in various diseases, such as autoimmune diseases, hypersensitivity, and cancer. The conjugation of small ubiquitin-related modifier (SUMO) is a post-translational protein modification that regulates activity, stability, and subcellular translocation of target proteins. In this study, CD8(+) T cells overexpressing SUMO2 showed greater proliferation and cytotoxic activity against tumor cells in the presence of IL-6 than wild-type CD8(+) T cells in vitro. These CD8(+) T cell functions were suppressed during treatment with MEK1 or PI3K-specific inhibitors. Therefore, our findings suggest that IL-6-derived signaling pathways, including the MEK1 and PI3K pathways, are upregulated by SUMO2 overexpression. However, transgenic expression of SUMO2 in T cells did not modulate Th1/2 balance. Collectively, our results showed that SUMO2-Tg promotes cytotoxic activity against tumor cells by increasing the proliferation and cytotoxicity of CD8(+) T cells.

Keywords: CD8+ T cells; Cytotoxicity; IL-6; Proliferation; SUMO2.

MeSH terms

  • Adaptive Immunity
  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cell Survival / immunology
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / immunology
  • Immunoglobulin E / blood
  • Interleukin-6 / immunology*
  • Interleukin-6 / pharmacology
  • Lymphocyte Activation / immunology
  • MAP Kinase Kinase 1 / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phosphatidylinositol 3-Kinases / metabolism
  • Small Ubiquitin-Related Modifier Proteins / genetics*
  • Small Ubiquitin-Related Modifier Proteins / immunology
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Interleukin-6
  • SUMO2 protein, mouse
  • Small Ubiquitin-Related Modifier Proteins
  • Immunoglobulin E
  • Phosphatidylinositol 3-Kinases
  • MAP Kinase Kinase 1
  • Map2k1 protein, mouse