Regulation in maintenance of remission involving the prognosis of a model of Multiple Sclerosis

维持缓解的调节涉及多发性硬化症模型的预后

• 批准号: 21790855
• 负责人: LIN Youwei
• 金额: $ 2.75万
• 依托单位: National Center of Neurology and Psychiatry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790855/
• 关键词: 神経病態免疫学; 制御性T細胞; 実験的自己免疫性脳脊髄炎; ペプチド優位性; 免疫学; 脳・神経疾患; 制御性細胞

Immunization with several encephalitogenic myelin peptides causes experimental autoimmune encephalomyelitis (EAE), resembling variety types of multiple sclerosis (MS).Noting that immunizing SJL/J mice with overlapping myelin proteolipid protein (PLP) residues 136-150 and 139-151 could induce quite different diseases ; monophasic EAE by PLP136-150 and relapsing EAE by PLP139-151, we found the non-genetic factors to maintain remission of EAE as follows : A) the hierarchy of the encephalitogenic peptide itself, which means that the more dominant peptide possessed the capacity to develop acute EAE, the less relapse and re-induction of EAE were occurred, and B) CD4^+CD25^+ regulatory T cells (Treg) induced in the lymphnodes during remission phase, which is characterized by maintenance at high level and by content of the highly potent Treg expressing both CD69 and CD103 (=DP-Treg). This DP-Treg can keep the property of Treg due to the low expression of IL-6R, nevertheless it shares some signatures with Th17, a pathogenic cause of EAE and MS, and may conduct regulatory function in situ.Furthermore, such regulation could be observed even under non-inflammatory condition, indicating the possibility of a potent and a safe autoimmune vaccination.

几种致脑髓磷脂肽免疫可引起实验性自身免疫性脑脊髓炎（EAE），类似于多种类型的多发性硬化症（MS）。注意到用重叠髓磷脂蛋白（PLP）残基136-150和139-151免疫SJL/J小鼠可诱导不同的疾病；PLP136-150的单相EAE和PLP139-151的复发性EAE，我们发现维持EAE缓解的非遗传因素如下：A)产脑肽本身的层次结构，即越占优势的肽具有发生急性EAE的能力，EAE复发和再诱导的发生越少；B)缓解期在淋巴结诱导CD4^+CD25^+调节性T细胞（Treg），其特征是维持在高水平，并且表达CD69和CD103的高效Treg含量（=DP-Treg）。由于IL-6R的低表达，该DP-Treg可以保持Treg的特性，但它与EAE和MS的致病因子Th17有一些共同的特征，可能在原位发挥调控功能。此外，即使在非炎症条件下也可以观察到这种调节，这表明可能存在有效和安全的自身免疫疫苗接种。

项目成果

実験的自己免疫性脳脊髄炎(EAE)の寛解維持に関わる制御機構

维持实验性自身免疫性脑脊髓炎（EAE）缓解的调节机制

• 发表时间: 2008
• 期刊: Neuroimmunology(日本神経免疫学会機関誌) 16-2
• 作者: 林幼偉

Dominancy of encephalitogenic peptide itself directs sustainable regulation of a model of multiple sclerosis, through induction of 'armoured' regulatory T cells

致脑炎肽本身的优势通过诱导“装甲”调节性 T 细胞指导多发性硬化症模型的可持续调节

• 发表时间: 2010
• 作者: Youwei Lin;Sachiko Miyake;Takashi Yamamura.;林幼偉
• 通讯作者: 林幼偉

誘導型制御性T細胞の特徴

诱导性调节性T细胞的特征

• 发表时间: 2007
• 期刊: 臨床免疫アレルギー科 48-5
• 作者: 林幼偉;山村隆
• 通讯作者: 山村隆

EAEの寛解を維持する機能的制御性T細胞の誘導に相関する脳炎惹起性ペプチドの優位性

致脑炎肽的优势与维持 EAE 缓解的功能性调节 T 细胞的诱导相关

• 发表时间: 2009
• 作者: 林幼偉;三宅幸子;山村隆
• 通讯作者: 山村隆

Dominancy of encephalitogenic peptide itself directs sustainable regulation of a model of multiple sclerosis, through induction of 'armoured' regulatory T cells.

致脑炎肽本身的优势通过诱导“装甲”调节性 T 细胞来指导多发性硬化症模型的可持续调节。

• 发表时间: 2010
• 作者: Youwei Lin;Sachiko Miyake;Takashi Yamamura.
• 通讯作者: Takashi Yamamura.