Feeding transgenic plants that express a tolerogenic fusion protein effectively protects against arthritis
2016 (English)In: Plant Biotechnology Journal, ISSN 1467-7644, E-ISSN 1467-7652, Vol. 14, no 4, 1106-1115 p.Article in journal (Refereed) Published
Although much explored, oral tolerance for treatment of autoimmune diseases still awaits the establishment of novel and effective vectors. We investigated if the tolerogenic CTA1(R7K)-COL-DD fusion protein can be expressed in edible plants and in this way induce oral tolerance and protect against arthritis. The fusion protein was recombinantly expressed in Arabidopsis thaliana plants, which were fed to H-2q restricted DBA/1 mice to assess the preventive effect on collagen-induced arthritis (CIA). The treatment resulted in fewer mice exhibiting disease and arthritis scores were significantly reduced. Immune suppression was evident in treated mice and serum biomarkers for inflammation as well as anti-collagen IgG responses were reduced. In spleen draining and lymph nodes, CD4+ T cell responses were reduced. Concomitant with a reduced effector T cell activity with lower IFNg, IL-13 and IL-17A production we observed an increase in IL-10 production to recall antigen stimulation in vitro, suggesting reduced Th1, Th2 and Th17 activity subsequent to upregulated IL-10 and regulatory T cell (Treg) functions. The present study shows that edible plants expressing a tolerogen were effective at stimulating CD4 T cell tolerance and in protecting against CIA disease. Our study conveys optimism as to the potential of using edible plants for oral treatment of rheumatoid arthritis.
Place, publisher, year, edition, pages
Wiley-Blackwell, 2016. Vol. 14, no 4, 1106-1115 p.
autoimmunity; transgenic plants; edible plants; CIA; IL-10; FoxP3
Immunology in the medical area Plant Biotechnology Biochemistry and Molecular Biology
Research subject Biochemistry; Immunology; Molecular Biology
IdentifiersURN: urn:nbn:se:oru:diva-45625DOI: 10.1111/pbi.12479ISI: 000373069400006PubMedID: 26403330ScopusID: 2-s2.0-84961215734OAI: oai:DiVA.org:oru-45625DiVA: diva2:847965
FunderSwedish Cancer SocietySwedish Research CouncilKnut and Alice Wallenberg FoundationAFA InsuranceEU, FP7, Seventh Framework ProgrammeSwedish Foundation for Strategic Research