Regulatory T cells promote myelin regeneration in the central nervous system.
Regulatory T cells promote myelin regeneration in the central nervous system.
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DOI：
10.1038/nn.4528
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发表时间：
2017-05
影响因子：
25
通讯作者：
Fitzgerald DC
中科院分区：
文献类型：
--
作者：
Dombrowski Y;O'Hagan T;Dittmer M;Penalva R;Mayoral SR;Bankhead P;Fleville S;Eleftheriadis G;Zhao C;Naughton M;Hassan R;Moffat J;Falconer J;Boyd A;Hamilton P;Allen IV;Kissenpfennig A;Moynagh PN;Evergren E;Perbal B;Williams AC;Ingram RJ;Chan JR;Franklin RJM;Fitzgerald DC
中枢神经系统（CNS）髓鞘的再生涉及从少突胶质细胞祖细胞（OPC）分化少突胶质细胞。在多发性硬化症（MS）中，尽管有丰富的OPC，但髓鞘再生可能失败，这表明少突胶质细胞分化受损。MS期间T细胞浸润CNS，但对T细胞在髓鞘再生中的功能知之甚少。在这里，我们报告说，调节性T细胞（Treg）促进少突胶质细胞分化和（重新）髓鞘。Treg缺陷小鼠表现出明显受损的髓鞘再生和少突胶质细胞分化，这是通过过继转移Treg来挽救的。在脑切片培养中，Treg加速了髓鞘形成和髓鞘再生，即使在没有明显炎症的情况下。Treg在体外直接促进OPC分化和髓鞘形成。我们确定CCN 3作为一种新的Treg衍生的介体的少突胶质细胞分化和髓鞘形成在体外。这些发现揭示了Treg在CNS中的新的再生功能，不同于免疫调节。虽然最初命名为“Treg”以反映免疫调节作用，但这也恰当地捕获了新兴的再生Treg功能。
Regeneration of central nervous system (CNS) myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells (OPC). In multiple sclerosis (MS), remyelination can fail despite abundant OPC, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS during MS, yet little is known about T cell functions in remyelination. Here, we report that regulatory T cells (Treg) promote oligodendrocyte differentiation and (re)myelination. Treg-deficient mice exhibited significantly impaired remyelination and oligodendrocyte differentiation that was rescued by adoptive transfer of Treg. In brain slice cultures, Treg accelerated developmental myelination and remyelination, even in the absence of overt inflammation. Treg directly promoted OPC differentiation and myelination in vitro. We identified CCN3 as a novel Treg-derived mediator of oligodendrocyte differentiation and myelination in vitro. These findings reveal a new regenerative function of Treg in the CNS, distinct from immunomodulation. Although originally named ‘Treg’ to reflect immunoregulatory roles, this also captures emerging, regenerative Treg functions aptly.