title: SUMO2 overexpression enhances the generation and function of interleukin-17-producing CD8⁺ T cells in mice.
abstract: 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)-γ and granzyme B mRNA levels. Although SUMO2 overexpression did not increase IFN-γ or granzyme B production in cytotoxic T lymphocytes, IL-12 treatment restored and increased IFN-γ 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-overexpressing T 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.
authors.affiliation: Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Tae Joon
authors.initials: TJ
authors.lastname: Won
authors.affiliation: Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Kyeong Eun
authors.initials: KE
authors.lastname: Hyung
authors.affiliation: Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Uy Dong
authors.initials: UD
authors.lastname: Sohn
authors.affiliation: College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Min
authors.affiliation: College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Do Ik
authors.initials: DI
authors.lastname: Lee
authors.affiliation: Pharmacognosy Lab, College of Pharmacy, Dankook University, Republic of Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea. Electronic address: khwang@cau.ac.kr.
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Hwang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D054407:Chemokine CCL4 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D009369:Neoplasms / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D020672:I-kappa B Proteins; D020381:Interleukin-17; D015850:Interleukin-6; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C515972:SUMO2 protein, mouse; D025841:Small Ubiquitin-Related Modifier Proteins; C494087:Stat3 protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D053804:Granzymes
keywords: Antitumor activity; IFN-γ; IL-17; STAT3; SUMO2; Tc17 cells