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

• Published in: Archives of pharmacal research Vol. 39; no. 5; pp. 705 - 712
• Main Authors: Lee, Yun-Jung, Won, Tae Joon, Hyung, Kyeong Eun, Jang, Ye Won, Kim, Soo Jeong, Lee, Do Ik, Park, So-Young, Hwang, Kwang Woo
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.05.2016; 대한약학회
• Subjects: 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; Male; MAP Kinase Kinase 1 - metabolism; Medicine; Mice, Inbred C57BL; Mice, Transgenic; Pharmacology/Toxicology; Pharmacy; Phosphatidylinositol 3-Kinases - metabolism; Research Article; Small Ubiquitin-Related Modifier Proteins - genetics; Small Ubiquitin-Related Modifier Proteins - immunology; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; 약학; Cytotoxicity; Proliferation; T cells; CD8; IL-6; SUMO2; CD8+ T cells
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-016-0736-6

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.