Transgenic rice seeds expressing altered peptide ligands against the M3 muscarinic acetylcholine receptor suppress experimental sialadenitis-like Sjogren’s syndrome
Transgenic rice seeds expressing altered peptide ligands against the M3 muscarinic acetylcholine receptor suppress experimental sialadenitis-like Sjogren’s syndrome
复制标题
转基因水稻种子表达针对 M3 毒蕈碱乙酰胆碱受体的改变的肽配体，抑制实验性唾液腺炎样干燥综合征
DOI：
10.1080/14397595.2019.1664368
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发表时间：
2019
影响因子：
2.2
通讯作者：
Sumida Takayuki
中科院分区：
文献类型：
--
作者：
Kudo Hanae;Tsuboi Hiroto;Asashima Hiromitsu;Takahashi Hiroyuki;Ono Yuko;Abe Saori;Honda Fumika;Kondo Yuya;Wakasa Yuhya;Takaiwa Fumio;Takano Makoto;Matsui Minoru;Matsumoto Isao;Sumida Takayuki
目的：我们先前报道了用M3毒蕈碱乙酰胆碱受体（M3 R）基因敲除小鼠的脾细胞接种Rag 1 −/−小鼠，M3 R肽混合物免疫小鼠，小鼠发生了涎腺炎样干燥综合征（M3 R诱导的涎腺炎[MIS]）。我们还发现，静脉内给予改变的肽配体（APL）的N-末端1（N1），这是一个T细胞表位的M3 R，抑制MIS。本研究旨在探讨表达N1-APL 7的水稻种子对MIS的抑制作用及其机制。方法：将表达N1和N1-APL 7的水稻种子口服给MIS小鼠2周。分析唾液流量和涎腺炎（唾液腺炎症）的变化。M3 R特异性T细胞反应在脾脏和调节分子在颈部淋巴结和肠系膜淋巴结的表达也analysed.Results：口服给药的N1-APL 7表达水稻种子显着恢复减少唾液流量和抑制sialadenitis相比，治疗与非转基因水稻种子和N1水稻种子。与其他组相比，在N1-APL 7大米处理组中，M3 R反应性T细胞的IFNγ产生倾向于下降。结论：口服N1-APL 7表达的水稻通过抑制M3 R特异性IFNγ和IL-17的产生以及通过增强调节分子的表达来抑制MIS。口服施用表达N1-APL 7的水稻种子显著恢复了唾液流量的减少，并通过抑制M3 R特异性IFNγ和IL-17的产生以及通过增强调节性T（Treg）细胞来抑制涎腺炎。
Objective:We previously reported thatRag1−/−mice inoculated with splenocytes from M3 muscarinic acetylcholine receptor (M3R) knockout mice immunized with an M3R peptide mixture developed sialadenitis-like Sjögren’s syndrome (M3R-induced sialadenitis [MIS]). We also found that intravenous administration of altered peptide ligand (APL) of N-terminal 1 (N1), which is one of the T-cell epitopes of M3R, suppressed MIS. In this study, we aimed to evaluate the suppressive ability and its mechanisms of rice seeds expressing N1-APL7 against MIS.Methods:Rice seeds expressing N1 and N1-APL7 were orally administered to MIS mice for 2 weeks. The changes in saliva flow and sialadenitis (salivary gland inflammation) were analyzed. The M3R-specific T-cell response in the spleen and the expression of regulatory molecules in the cervical lymph nodes and mesenteric lymph nodes were also analyzed.Results:Oral administration of N1-APL7-expressing rice seeds significantly recovered reduction in saliva flow and suppressed sialadenitis when compared with treatment with nontransgenic rice seeds and N1 rice seeds. IFNγ production from M3R-reactive T cells tended to decline in the N1-APL7 rice-treated group as compared with those in the other groups. In the N1-APL7 rice-treated group, the mRNA expression levels ofFoxp3in the cervical-lymph-node CD4+T cells were higher than those in the other groups.Conclusion:Oral administration of N1-APL7-expressing rice suppressed MIS via suppression of M3R-specific IFNγ and IL-17 production and via enhancement of regulatory molecule expression.Key messagesWe generated N1-peptide- or N1-APL7-expressing rice seeds. Oral administration of N1-APL7-expressing rice seeds significantly recovered the reduction of saliva flow and suppressed sialadenitis via the suppression of M3R specific IFNγ and IL-17 production and via enhancement of regulatory T (Treg) cells.