Open AccessSuppression of collagen‐induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of type II collagen
Author(s) -
Iizuka Mana,
Wakasa Yuhya,
Tsuboi Hiroto,
Asashima Hiromitsu,
Hirota Tomoya,
Kondo Yuya,
Matsumoto Isao,
Takaiwa Fumio,
Sumida Takayuki
Publication year - 2014
Publication title -
plant biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.525
H-Index - 115
eISSN - 1467-7652
pISSN - 1467-7644
DOI - 10.1111/pbi.12223
Subject(s) - type ii collagen , arthritis , transgene , foxp3 , biology , genetically modified rice , ovalbumin , immunology , autoimmune disease , immune system , rheumatoid arthritis , medicine , antibody , genetically modified crops , biochemistry , gene
Summary 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 ( APL s) of type II collagen ( CII 256‐271) suppress the development of collagen‐induced arthritis ( CIA ). In this study, we generated transgenic rice expressing CII 256‐271 and APL 6 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 APL 6 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 ( iLN s), 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 APL s of type II collagen on the autoimmune disease CIA , suggesting that the seed‐based mucosal vaccine against CIA functions via a unique mechanism.