Journal
CELLULAR SIGNALLING
Volume 27, Issue 6, Pages 1246-1252Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2015.03.001
Keywords
SUMO2; Tc17 cells; IL-17; IFN-gamma; STAT3; Antitumor activity
Categories
Funding
- Postdoctoral Research Program of Chung-Ang University
- Public Welfare & Safety Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2010-0020842]
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Small ubiquitin-like modifier (SUMO) 2 is a small protein that controls the activity and stability of other proteins by SUMOylation. In this study, T cell-specific SUMO2 overexpressing transgenic mice were generated to study the effect of SUMO2 on T lymphocytes. SUMO2 overexpression promoted differentiation of interleukin (IL)-17-producing CD8(+) T cells, and significantly suppressed the growth of EL4 tumor cells in vivo. Moreover, the tumor tissue from SUMO2-overexpressing mice had higher interferon (IFN)-gamma and granzyme B mRNA levels. Although SUMO2 overexpression did not increase IFN-gamma or granzyme B production in cytotoxic T lymphocytes, IL-12 treatment restored and increased IFN-gamma secretion in IL-17-producing CD8(+) T cells. SUMO2 overexpression also increased gene expression of chemokines, CCL4, and CXCL10, which attract cytotoxic T lymphocytes to tumor tissues. Additionally, SUMO2-overexpressingT cells exhibited increased STAT3 phosphorylation, implying a SUMO2 target which up-regulates STAT3 activity governing IL-17A-producing CD8(+) T cell differentiation and antitumor immune responses. (C) 2015 Published by Elsevier Inc.
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