Exosomes released by islet-derived mesenchymal stem cells trigger autoimmune responses in NOD mice.
Exosomes released by islet-derived mesenchymal stem cells trigger autoimmune responses in NOD mice.
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作者：
Rahman MJ;Regn D;Bashratyan R;Dai YD
外泌体（Exosomes，EXO）是一种分泌的纳米级膜囊泡，含有有效的免疫刺激物质。我们最近证明，胰岛素瘤释放的EXO可以刺激非肥胖糖尿病（NOD）小鼠（1型糖尿病的自发性疾病模型）的自身免疫反应。为了研究原代胰岛细胞是否可以产生EXO，我们从NOD小鼠的胰岛中分离细胞并在体外培养。有趣的是，培养的胰岛释放成纤维细胞样的快速复制细胞，表达间充质干细胞（MSC）标志物，包括CD 105和干细胞抗原-1。这些胰岛MSC样细胞释放高度免疫刺激性的EXO，其可以激活NOD小鼠中内源性引发的自身反应性B和T细胞。血清EXO水平和EXO诱导的干扰素-γ产生与糖尿病前期早期疾病进展呈正相关。与这些观察结果一致，胰腺的免疫组织学分析显示，在正常胰岛中，CD 105+细胞局限于胰岛周围区域，但随着淋巴细胞浸润的发生，CD 105+细胞渗透到β细胞区域。用EXO免疫促进了转移的致糖尿病T细胞的扩增，并加速了效应T细胞介导的胰岛破坏。因此，EXO可能是自身抗原的载体，具有强大的佐剂活性，并可能在NOD小鼠中起自身免疫触发剂的作用。
Exosomes (EXOs) are secreted, nano-sized membrane vesicles that contain potent immunostimulatory materials. We have recently demonstrated that insulinoma-released EXOs can stimulate the autoimmune responses in nonobese diabetic (NOD) mice, a spontaneous disease model for type 1 diabetes. To investigate whether primary islet cells can produce EXOs, we isolated cells from the islet of Langerhans of NOD mice and cultured them in vitro. Interestingly, cultured islets release fibroblast-like, fast-replicating cells that express mesenchymal stem cell (MSC) markers, including CD105 and stem-cell antigen-1. These islet MSC–like cells release highly immunostimulatory EXOs that could activate autoreactive B and T cells endogenously primed in NOD mice. Serum EXO levels and EXO-induced interferon-γ production were positively correlated with disease progression at the early prediabetic stage. Consistent with these observations, immunohistological analysis of pancreata showed that CD105+ cells are restricted to the peri-islet area in normal islets but penetrate into the β-cell area as lymphocyte infiltration occurs. Immunization with EXOs promoted expansion of transferred diabetogenic T cells and accelerated the effector T cell–mediated destruction of islets. Thus, EXOs could be the autoantigen carrier with potent adjuvant activities and may function as the autoimmune trigger in NOD mice.
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DOI：
10.4049/jimmunol.0803543
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Melli K;Friedman RS;Martin AE;Finger EB;Miao G;Szot GL;Krummel MF;Tang Q
通讯作者：
Tang Q
通过在胰腺淋巴结中发育调节的胰岛细胞抗原的发育表现来启动自身免疫性糖尿病。
DOI：
10.1084/jem.189.2.331
发表时间：
1999-01-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Höglund P;Mintern J;Waltzinger C;Heath W;Benoist C;Mathis D
通讯作者：
Mathis D
DOI：
10.4049/jimmunol.0900803
发表时间：
2009-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fiorina P;Jurewicz M;Augello A;Vergani A;Dada S;La Rosa S;Selig M;Godwin J;Law K;Placidi C;Smith RN;Capella C;Rodig S;Adra CN;Atkinson M;Sayegh MH;Abdi R
通讯作者：
Abdi R
DOI：
10.1073/pnas.0604317103
发表时间：
2006-08-15
影响因子：
11.1
作者：
Chaparro, Rodolfo Jose;Konigshofer, Yves;Chien, Yueh-hsiu
通讯作者：
Chien, Yueh-hsiu
影响因子：
4.8
作者：
Guz, Y;Nasir, I;Teitelman, G
通讯作者：
Teitelman, G