title: Knockdown of core 1 beta 1, 3-galactosyltransferase prolongs skin allograft survival with induction of galectin-1 secretion and suppression of CD8+ T cells: T synthase knockdown effects on galectin-1 and CD8+ T cells.
abstract: Core 1 beta 1,3-galactosyltransferase also known as T-antigen-synthase or T-synthase is a key enzyme for the synthesis of the common core 1 O-glycan structure (T-antigen). Although T-synthase is known to be important in human immune-related diseases, the effects of T-synthase and T-antigen on host immune responses remain poorly defined. In this study, a T-synthase-specific short hairpin RNA (shRNA) was transfected into murine colon carcinoma CT26 cells or mouse muscle tissues via intramuscular electroporation to assess the effects of T-synthase on T cells and cytokines. T-synthase knockdown significantly induced galectin-1 secretion both in vivo and in vitro and strongly enhanced Th2 cytokine (IL-10 and IL-4) production in vivo. Further, the increased production of galectin-1 induced by T-synthase knockdown promoted CD8(+) T-cell apoptosis, which, when combined with the increased production of CD4(+) T cell-derived Th2 cytokines prolonged the survival of skin allografts in mice. Our data suggest core 1 beta 1,3-galactosyltransferase-shRNA could serve not only as a useful tool in organ transplantation but also as a powerful tool for investigating O-glycans and glycoprotein synthesis and function.
authors.affiliation: Department of Immunology and State Key Laboratory of Virology, Wuhan University School of Medicine, Wuhan, 430071, People's Republic of China.
authors.forename: Hai-Dan
authors.initials: HD
authors.lastname: Chen
authors.forename: Xia
authors.initials: X
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Yu
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Zhao
authors.forename: Yushan
authors.initials: Y
authors.lastname: Ren
authors.forename: Yi-Dan
authors.initials: YD
authors.lastname: Zhou
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.forename: Xiao-Lian
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D005700:Galactosyltransferases / Q000235:genetics* / Q000378:metabolism*; D037483:Galectin 1 / Q000378:metabolism*; D006085:Graft Survival; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D034741:RNA, Small Interfering; D012867:Skin / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D037483:Galectin 1; D034741:RNA, Small Interfering; D016753:Interleukin-10; D015847:Interleukin-4; D005700:Galactosyltransferases; C076385:glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase