title: A Trichosanthin-derived peptide suppresses type 1 immune responses by TLR2-dependent activation of CD8(+)CD28(-) Tregs.
abstract: A group of 15-aa-long Trichosanthin-derived peptides was synthesized and screened based on their differential abilities to induce low-responsiveness in mouse strains with high and low susceptibility. One of them was conjugated to form a homo-tetramer Tk-tPN. At concentrations of 0.1-50 μg/ml, Tk-tPN activated CD8(+)CD28(-) Tregs in vitro to induce immune suppression as effectively as the native Trichosanthin but did not exhibit cytotoxicity. In EAE mice which were pre-treated with Tk-tPN or Tk-tPN-activated CD8(+) T cells, a marked attenuation of clinical scores was recorded together with an expansion of the CD8(+)CD28(-) Treg from 2.2% to 36.1% in vivo. A pull-down assay and signal transduction analyses indicated that the ability of Tk-tPN to convert the CD8(+)CD28(-) Treg-related cytokine secretion pattern from type 1 to type 2 depends on the TLR2-initiated signaling in macrophages. The high production of IL-4/IL-10 by the Tk-tPN-activated CD8(+)CD28(-) Treg suggests the value of using Tk-tPN as a therapeutic reagent for Th1-dominant immunological diseases.
authors.affiliation: Department of Immunology, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Neng
authors.initials: N
authors.lastname: Yang
authors.affiliation: Shanghai Institute of Immunology, Shanghai 200025, China.
authors.forename: Zuoqing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Shanghai Institute of Immunology, Shanghai 200025, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Jiao
authors.affiliation: Department of Immunology, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gu
authors.affiliation: Shanghai Institute of Immunology, Shanghai 200025, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Shanghai Institute of Immunology, Shanghai 200025, China. Electronic address: lulunew2003@163.com.
authors.forename: Liming
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Immunology, Shanghai Jiaotong University School of Medicine, China. Electronic address: my@shsmu.edu.cn.
authors.forename: Kuang-Yen
authors.initials: KY
authors.lastname: Chou
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015978:Trichosanthin / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology
chemical_list: D018106:CD28 Antigens; D016827:CD8 Antigens; D010455:Peptides; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D016753:Interleukin-10; D015847:Interleukin-4; D015978:Trichosanthin
keywords: CD8(+)CD28(−) Treg; EAE; TLR2 signaling; Trichosanthin-derived peptide