title: Suppression of collagen-induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of type II collagen.
abstract: Rheumatoid arthritis (RA) is an autoimmune disease associated with the recognition of self proteins secluded in arthritic joints. We previously reported that altered peptide ligands (APLs) of type II collagen (CII256-271) suppress the development of collagen-induced arthritis (CIA). In this study, we generated transgenic rice expressing CII256-271 and APL6 contained in fusion proteins with the rice storage protein glutelin in the seed endosperm. These transgene products successfully and stably accumulated at high levels (7-24 mg/g seeds) in protein storage vacuoles (PB-II) of mature seeds. We examined the efficacy of these transgenic rice seeds by performing oral administration of the seeds to CIA model mice that had been immunized with CII. Treatment with APL6 transgenic rice for 14 days significantly inhibited the development of arthritis (based on clinical score) and delayed disease onset during the early phase of arthritis. These effects were mediated by the induction of IL-10 from CD4(+ ) CD25(-) T cells against CII antigen in splenocytes and inguinal lymph nodes (iLNs), and treatment of APL had no effect on the production of IFN-γ, IL-17, IL-2 or Foxp3(+) Treg cells. These findings suggest that abnormal immune suppressive mechanisms are involved in the therapeutic effect of rice-based oral vaccine expressing high levels of APLs of type II collagen on the autoimmune disease CIA, suggesting that the seed-based mucosal vaccine against CIA functions via a unique mechanism.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Mana
authors.initials: M
authors.lastname: Iizuka
authors.forename: Yuhya
authors.initials: Y
authors.lastname: Wakasa
authors.forename: Hiroto
authors.initials: H
authors.lastname: Tsuboi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Asashima
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hirota
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kondo
authors.forename: Isao
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Fumio
authors.initials: F
authors.lastname: Takaiwa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008024:Ligands; D051379:Mice; D008811:Mice, Inbred DBA; D012275:Oryza / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D030821:Plants, Genetically Modified
chemical_list: D024043:Collagen Type II; D016207:Cytokines; D008024:Ligands; D010455:Peptides
keywords: altered peptide ligands; glutelin; rheumatoid arthritis; transgenic rice seed; type II collagen