Dendritic cells ameliorate autoimmunity in the CNS by controlling the homeostasis of PD-1 receptor(+) regulatory T cells.
Dendritic cells ameliorate autoimmunity in the CNS by controlling the homeostasis of PD-1 receptor(+) regulatory T cells.
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DOI：
10.1016/j.immuni.2012.05.025
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发表时间：
2012-08
期刊：
影响因子：
32.4
通讯作者：
Nir Yogev;Friederike Frommer;D. Lukas;Kordula Kautz-Neu;K. Karram;D. Ielo;E. von Stebut;H. Probst-H.-Probs
中科院分区：
文献类型：
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作者：
Nir Yogev;Friederike Frommer;D. Lukas;Kordula Kautz-Neu;K. Karram;D. Ielo;E. von Stebut;H. Probst-H.-Probs
成熟的树突状细胞（DCs）在免疫应答的启动中被确立为无可匹敌的抗原呈递细胞（APC），而稳态DCs诱导外周T细胞耐受。使用各种遗传方法，我们耗尽小鼠中的CD 11 c +DCs并诱导自身免疫性CNS炎症。出乎意料的是，与对照小鼠相比，缺乏DC的小鼠发展出加重的疾病。此外，当我们设计DC以诱导方式呈递CNS相关自身抗原时，我们发现了预防疾病的强大耐受性，这与抗原特异性T细胞上PD-1受体的上调相一致。此外，我们发现PD-1对于DC介导的调节性T细胞的诱导是必需的。我们的研究结果表明，DC的减少干扰耐受性，导致更强的炎症反应，并且其他APC群体可以补偿DC耗尽小鼠中免疫原性APC功能的丧失。
Mature dendritic cells (DCs) are established as unrivaled antigen-presenting cells (APCs) in the initiation of immune responses, whereas steady-state DCs induce peripheral T cell tolerance. Using various genetic approaches, we depleted CD11c+DCs in mice and induced autoimmune CNS inflammation. Unexpectedly, mice lacking DCs developed aggravated disease compared to control mice. Furthermore, when we engineered DCs to present a CNS-associated autoantigen in an induced manner, we found robust tolerance that prevented disease, which coincided with an upregulation of the PD-1 receptor on antigen-specific T cells. Additionally, we showed that PD-1 was necessary for DC-mediated induction of regulatory T cells. Our results show that a reduction of DCs interferes with tolerance, resulting in a stronger inflammatory response, and that other APC populations could compensate for the loss of immunogenic APC function in DC-depleted mice.