Functional characterization of the dural sinuses as a neuroimmune interface.
Functional characterization of the dural sinuses as a neuroimmune interface.
复制标题
硬脑膜窦作为神经免疫界面的功能特征。
DOI：
10.1016/j.cell.2020.12.040
复制
发表时间：
2021-02-18
期刊：
影响因子：
64.5
通讯作者：
Kipnis J
中科院分区：
文献类型：
--
作者：
Rustenhoven J;Drieu A;Mamuladze T;de Lima KA;Dykstra T;Wall M;Papadopoulos Z;Kanamori M;Salvador AF;Baker W;Lemieux M;Da Mesquita S;Cugurra A;Fitzpatrick J;Sviben S;Kossina R;Bayguinov P;Townsend RR;Zhang Q;Erdmann-Gilmore P;Smirnov I;Lopes MB;Herz J;Kipnis J
尽管建立了中枢神经系统（CNS）免疫豁免的教条，神经免疫相互作用在各种神经系统疾病中发挥着积极的作用。然而，中枢神经系统免疫监视的精确机制仍然难以捉摸;特别是，外周适应性免疫可以采样CNS衍生抗原的解剖部位以及协调这种监视的细胞和分子介质。在这里，我们证明，CNS衍生的抗原在脑脊液（CSF）周围的硬脑膜窦积累，被捕获的局部抗原呈递细胞，并提出巡逻的T细胞。这种监视是由形成窦间质龛的内皮细胞和壁细胞实现的。T细胞识别CSF来源的抗原在这个网站上促进组织驻留表型和效应器功能的硬脑膜内。这些发现突出了硬脑膜窦作为神经免疫界面的关键作用，在稳态条件下对脑抗原进行了调查，并阐明了多发性硬化症动物模型中与年龄相关的功能障碍和神经炎症发作。Rustenhoven等人将硬脑膜窦确定为神经免疫界面，其中巡逻T细胞调查脑和CSF来源的抗原以实现CNS免疫监视。这种生态位在衰老和神经炎症过程中发生变化，可能代表神经系统疾病的新治疗靶点。
Despite the established dogma of central nervous system (CNS) immune privilege, neuroimmune interactions play an active role in diverse neurological disorders. However, the precise mechanisms underlying CNS immune surveillance remain elusive; particularly, the anatomical sites where peripheral adaptive immunity can sample CNS-derived antigens and the cellular and molecular mediators orchestrating this surveillance. Here, we demonstrate that CNS-derived antigens in the cerebrospinal fluid (CSF) accumulate around the dural sinuses, are captured by local antigen-presenting cells, and presented to patrolling T cells. This surveillance is enabled by endothelial and mural cells forming the sinus stromal niche. T cell recognition of CSF-derived antigens at this site promoted tissue resident phenotypes and effector functions within the dural meninges. These findings highlight the critical role of dural sinuses as a neuroimmune interface, where brain antigens are surveyed under steady-state conditions, and shed light on age-related dysfunction and neuroinflammatory attack in animal models of multiple sclerosis. Rustenhoven et al. identify the dural sinuses as a neuroimmune interface, where patrolling T cells survey brain- and CSF- derived antigens to enable CNS immune surveillance. This niche is altered during aging and neuroinflammation and may represent a new therapeutic target for neurological diseases.
登录
查看更多内容
影响因子：
64.8
作者：
Filiano AJ;Xu Y;Tustison NJ;Marsh RL;Baker W;Smirnov I;Overall CC;Gadani SP;Turner SD;Weng Z;Peerzade SN;Chen H;Lee KS;Scott MM;Beenhakker MP;Litvak V;Kipnis J
通讯作者：
Kipnis J
脑膜免疫调节学习和记忆：IL-4 的关键作用。
影响因子：
15.3
作者：
Derecki, Noel C.;Cardani, Amber N.;Yang, Chun Hui;Quinnies, Kayla M.;Crihfield, Anastasia;Lynch, Kevin R.;Kipnis, Jonathan
通讯作者：
Kipnis, Jonathan
影响因子：
30.5
作者：
Alves de Lima K;Rustenhoven J;Da Mesquita S;Wall M;Salvador AF;Smirnov I;Martelossi Cebinelli G;Mamuladze T;Baker W;Papadopoulos Z;Lopes MB;Cao WS;Xie XS;Herz J;Kipnis J
通讯作者：
Kipnis J
影响因子：
4.3
作者：
Chen H;Lau MC;Wong MT;Newell EW;Poidinger M;Chen J
通讯作者：
Chen J
影响因子：
4.4
作者：
Erde, Jonathan;Loo, Rachel R. Ogorzalek;Loo, Joseph A.
通讯作者：
Loo, Joseph A.