A Study of the Regulation of Dendritic Cells and Immunological Memory by Immunoglobulins in Multiple Sclerosis

多发性硬化症中免疫球蛋白对树突状细胞和免疫记忆的调节研究

• 批准号: 18590923
• 负责人: FUJIHARA Kazuo
• 金额: $ 2.43万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590923/
• 关键词: Multiple Sclerosis; Demyelinating Disease; Immunoglobulin; Dendritic Cell

Intravenous immunoglobulin preparations (IVIg) are reportedly effective in inhibiting the relapseof multiple sclerosis (MS), but few reports have investigated the effect of IVIg on dendritic cells (DCs), which are thought to be involved in such relapses. Using a system that uses monokines to differentiate DCs from peripheral blood monocytes (Mo-DCs), we investigated the effect of Immunoglobulin G (IgG) on these antigen-presenting cells. Treatment of monocytes derived from a healthy volunteer with IgG partially inhibited the expression of CD1a, a marker of immature DCs (imDCs), and CD40 and CD80, which are markers associated with T cell activation. In contrast, IgG treatment enhanced the expression of CD83, a marker of mature DCs (mDCs). IgG markedly inhibited the expression of CD49d [very late activation antigen (VLA)-4 〓4-integrin], the adhesion molecule required for mDCs to cross the blood brain barrier (BBB). As neutralizing antibodies against CD49d have a therapeutic effect on MS, we investigated the effect of IgG on Mo-DCs derived from the peripheral blood of relapsing-remitting MS patients. We obtained similar results in both MS patients and healthy controls. In addition, IgG treatment of cells from both healthy controls and MS patients inhibited the production of interleukin (IL)-12, a cytokine associated with mDC maturation, but did not inhibit the production of IL-10. These results suggested the possibility that IgG treatment, apart from its known ability to regulate inflammation, may help prevent relapses of MS by controlling DC maturation, consequently inhibiting invasion of the central nervous system and affecting the cytokine profile.

静脉注射免疫球蛋白制剂（IVIg）据报道可有效抑制多发性硬化（MS）的复发，但很少有报道研究IVIg对树突状细胞（DC）的作用，而DC被认为与MS的复发有关。使用一个系统，使用单核细胞分化树突状细胞从外周血单核细胞（Mo-DCs），我们研究了免疫球蛋白G（IgG）对这些抗原呈递细胞的影响。用IgG处理来自健康志愿者的单核细胞部分抑制了未成熟DC（imDC）的标志物CD 1a以及与T细胞活化相关的标志物CD 40和CD 80的表达。相反，IgG处理增强了成熟DC（mDC）的标志物CD 83的表达。IgG显著抑制CD 49 d [极晚期活化抗原（VLA）-4 β 4-整合素]的表达，CD 49 d是mDC穿过血脑屏障（BBB）所需的粘附分子。由于抗CD 49 d的中和抗体对MS具有治疗效果，我们研究了IgG对来自复发缓解型MS患者外周血的Mo-DCs的作用。我们在MS患者和健康对照中获得了相似的结果。此外，来自健康对照和MS患者的细胞的IgG处理抑制了白细胞介素（IL）-12（一种与mDC成熟相关的细胞因子）的产生，但不抑制IL-10的产生。这些结果表明，IgG治疗的可能性，除了其已知的调节炎症的能力，可能有助于防止MS的复发，通过控制DC成熟，从而抑制中枢神经系统的侵袭和影响细胞因子谱。

项目成果

Demyelinating Disease

• DOI: 10.1007/978-3-030-39903-0_300481
• 发表时间: 2020
• 期刊: Encyclopedia of Behavioral Medicine
• 作者: Richard Camara

二次進行型多発性硬化症

继发性进行性多发性硬化症

• 发表时间: 2007
• 期刊: Current Insights in Neurological Science 16
• 作者: 松尾友仁;進藤美恵子;小川秀一郎;栗崎宏憲;永淵正法;藤原一男
• 通讯作者: 藤原一男

Multiple Sclerosis in Japan: recent perspectives on clinical subtypes and pathogenesis

日本多发性硬化症：临床亚型和发病机制的最新观点

• 发表时间: 2006
• 作者: 長谷川 一宏、脇野 修;他;Fujihara K
• 通讯作者: Fujihara K

Neuromyelitis Optica: the concept, pathogenesis and therapy

视神经脊髓炎：概念、发病机制和治疗

• 发表时间: 2007
• 作者: Wakino;S;Itoh;H;Fujihara K.
• 通讯作者: Fujihara K.

NMO, MS and Plasmapheresis in Japan

日本的 NMO、MS 和血浆去除术

• 发表时间: 2007
• 作者: Oyanagi K;Nagasao J;Yamazaki M;Okamoto K;Aoki M;Watabe K;Wada M;Morita T;Takahashi H;Mizutani T;Hayashi H;Fujihara K
• 通讯作者: Fujihara K