title: Suppression of glucose-6-phosphate-isomerase induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of glucose-6-phosphate-isomerase.
abstract: OBJECTIVE
  To investigate the effects of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (hGPI325-339) in mice model of GPI-induced arthritis (GIA).
  
  
  METHODS
  We generated transgenic rice expressing T-cell epitope of hGPI325-339and APL12 contained in the seed endosperm. The transgenic rice seeds were orally administered prophylactically before the induction of GIA. The severity of arthritis and titers of serum anti-GPI antibodies were evaluated. We examined for IL-17 production in splenocytes and inguinal lymph node (iLN) cells, and analyzed the expression levels of functional molecules in splenocytes.
  
  
  RESULTS
  Prophylactic treatment of GIA mice with APL12 transgenic (APL12-TG) rice seeds significantly reduced the severity of arthritis and titers of serum anti-GPI antibodies compared with non-transgenic (Non-TG) rice-treated mice. APL12-TG and hGPI325-339transgenic (hGPI325-339-TG) rice seeds improved the histopathological arthritis scores and decreased IL-17 production compared with non-TG rice-treated mice. APL12-TG rice-treated GIA mice showed upregulation of Foxp3 and GITR protein in CD4+CD25+Foxp3+cells in the spleen compared with non-TG rice- and hGPI325-339-TG rice-treated mice.
  
  
  CONCLUSIONS
  APL12-TG rice seeds improved the severity of GIA through a decrease in production of IL-17 and anti-GPI antibodies via upregulation of Foxp3 and GITR expression on Treg cells in spleen.
authors.affiliation: a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba , Ibaraki , Japan and.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hirota
authors.affiliation: a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba , Ibaraki , Japan and.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Tsuboi
authors.affiliation: a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba , Ibaraki , Japan and.
authors.forename: Mana
authors.initials: M
authors.lastname: Iizuka-Koga
authors.affiliation: a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba , Ibaraki , Japan and.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba , Ibaraki , Japan and.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Asashima
authors.affiliation: a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba , Ibaraki , Japan and.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yokosawa
authors.affiliation: a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba , Ibaraki , Japan and.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: b Functional Transgenic Crops Research Unit , National Institute of Agrobiological Sciences , Tsukuba , Ibaraki , Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ohta
authors.affiliation: b Functional Transgenic Crops Research Unit , National Institute of Agrobiological Sciences , Tsukuba , Ibaraki , Japan.
authors.forename: Yuhya
authors.initials: Y
authors.lastname: Wakasa
authors.affiliation: a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba , Ibaraki , Japan and.
authors.forename: Isao
authors.initials: I
authors.lastname: Matsumoto
authors.affiliation: b Functional Transgenic Crops Research Unit , National Institute of Agrobiological Sciences , Tsukuba , Ibaraki , Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Takaiwa
authors.affiliation: a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba , Ibaraki , Japan and.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001168:Arthritis / Q000628:therapy*; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D008024:Ligands; D051379:Mice; D008811:Mice, Inbred DBA; D012275:Oryza / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012639:Seeds / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008024:Ligands; D010455:Peptides; C554959:GPI protein, human; D005956:Glucose-6-Phosphate Isomerase
keywords: Altered peptide ligands; arthritis; glucose-6-phosphate-isomerase