Dendritic cells tip the balance towards induction of regulatory T cells upon priming in experimental autoimmune encephalomyelitis.
Dendritic cells tip the balance towards induction of regulatory T cells upon priming in experimental autoimmune encephalomyelitis.
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DOI：
10.1016/j.jaut.2016.09.008
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发表时间：
2017
影响因子：
12.8
通讯作者：
M. Paterka;J. Voss;Johannes Werr;E. Reuter;S. Franck;Tina Leuenberger;J. Herz;H. Radbruch;T. Bopp;Volker Siffrin;F. Zipp
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文献类型：
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作者：
M. Paterka;J. Voss;Johannes Werr;E. Reuter;S. Franck;Tina Leuenberger;J. Herz;H. Radbruch;T. Bopp;Volker Siffrin;F. Zipp
平衡调节机制，如调节性T细胞（Treg）的诱导，限制了神经炎症中自身免疫攻击的作用。然而，树突状细胞（DC）作为最强大的抗原呈递细胞，这是在这种情况下有趣的治疗靶点的作用，并没有完全理解。在这里，我们证明了在实验性自身免疫性脑脊髓炎（EAE）中髓鞘特异性T细胞的引发阶段，条件性消融DC选择性地中止诱导型Treg（iTreg）诱导，而辅助性T细胞（Th）1/17细胞的生成没有改变。由于强增殖反应，DC通过产生具有高水平白细胞介素（IL）-2的环境来促进iTreg诱导。在不存在DC的情况下，B220+B细胞代替抗原呈递细胞（APC）接管Th 17细胞的引发，但不诱导iTreg，从而导致不受调节的严重自身免疫。
Counter-balancing regulatory mechanisms, such as the induction of regulatory T cells (Treg), limit the effects of autoimmune attack in neuroinflammation. However, the role of dendritic cells (DCs) as the most powerful antigen-presenting cells, which are intriguing therapeutic targets in this context, is not fully understood. Here, we demonstrate that conditional ablation of DCs during the priming phase of myelin-specific T cells in experimental autoimmune encephalomyelitis (EAE) selectively aborts inducible Treg (iTreg) induction, whereas generation of T helper (Th)1/17 cells is unaltered. DCs facilitate iTreg induction by creating a milieu with high levels of interleukin (IL)-2 due to a strong proliferative response. In the absence of DCs, B220+B cells take over priming of Th17 cells in the place of antigen-presenting cells (APCs), but not the induction of iTreg, thus leading to unregulated, severe autoimmunity.