Feeding transgenic plants that express a tolerogenic fusion protein effectively protects against arthritis
Feeding transgenic plants that express a tolerogenic fusion protein effectively protects against arthritis
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DOI：
10.1111/pbi.12479
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发表时间：
2016-04-01
影响因子：
13.8
通讯作者：
Lycke, Nils Y.
中科院分区：
文献类型：
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作者：
Hansson, Charlotta;Schon, Karin;Lycke, Nils Y.
尽管已经进行了很多探索，但用于治疗自身免疫性疾病的口服耐受仍有待于建立新的和有效的载体。我们研究了致耐受性CTA 1（R7 K）-COL-DD融合蛋白是否可以在可食用植物中表达，以诱导口服耐受并预防关节炎。在拟南芥中重组表达融合蛋白，并将其喂给H-2（q）限制性DBA/1小鼠，以评估其对胶原诱导的关节炎（CIA）的预防作用。治疗导致更少的小鼠表现出疾病和关节炎评分显着降低。免疫抑制在治疗的小鼠中是明显的，并且炎症的血清生物标志物以及抗胶原IgG应答降低。在脾脏和引流淋巴结中，CD 4（+）T细胞反应降低。伴随着效应T细胞活性降低和IFN、IL-13和IL-17 A产生降低，我们观察到IL-10产生增加以体外回忆抗原刺激，表明在上调IL-10和调节性T细胞（Treg）功能之后Th 1、Th 2和Th 17活性降低。这项研究表明，表达耐受原的可食用植物在刺激CD 4 T细胞耐受性和预防CIA疾病方面是有效的。我们的研究传达了乐观的潜力，使用可食用植物口服治疗类风湿性关节炎。
Although much explored, oral tolerance for treatment of autoimmune diseases still awaits the establishment of novel and effective vectors. We investigated whether the tolerogenic CTA1(R7K)-COL-DD fusion protein can be expressed in edible plants, to induce oral tolerance and protect against arthritis. The fusion protein was recombinantly expressed in Arabidopsis thaliana plants, which were fed to H-2(q)-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 anticollagen IgG responses were reduced. In spleen and draining lymph nodes, CD4(+) T-cell responses were reduced. Concomitant with a reduced effector T-cell activity with lower IFN, IL-13 and IL-17A production, we observed an increase in IL-10 production to recall antigen stimulation invitro, suggesting reduced Th1, Th2 and Th17 activity subsequent to up-regulated IL-10 and regulatory T-cell (Treg) functions. This 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.