Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells.
Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells.
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DOI：
10.1038/ncomms11626
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发表时间：
2016-05-18
影响因子：
16.6
通讯作者：
Meuth SG
中科院分区：
文献类型：
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作者：
Göbel K;Pankratz S;Asaridou CM;Herrmann AM;Bittner S;Merker M;Ruck T;Glumm S;Langhauser F;Kraft P;Krug TF;Breuer J;Herold M;Gross CC;Beckmann D;Korb-Pap A;Schuhmann MK;Kuerten S;Mitroulis I;Ruppert C;Nolte MW;Panousis C;Klotz L;Kehrel B;Korn T;Langer HF;Pap T;Nieswandt B;Wiendl H;Chavakis T;Kleinschnitz C;Meuth SG
异常免疫应答代表中枢神经系统（CNS）自身免疫的根本原因，包括多发性硬化（MS）。最近的证据表明，在CNS自身免疫中，凝血和免疫之间存在串扰。在这里，我们确定凝血因子XII（FXII），内源性凝血级联反应和激肽释放酶-激肽系统的启动子，作为一种特异性免疫细胞调节剂。在复发期间MS患者的血浆中存在高水平的FXII活性。FXII的缺乏或药理学阻断使小鼠对实验性自身免疫性脑脊髓炎（MS的模型）不太敏感，并且伴随着产生白细胞介素-17A的T细胞的数量减少。FXII的免疫激活由树突状细胞以CD 87依赖性方式介导，并涉及细胞内环AMP形成的改变。我们的研究表明，血浆凝血级联的成员是自身免疫的关键介质。FXII抑制可提供对抗MS和其他免疫相关疾病的策略。 因子XII启动内源性凝血级联和激肽系统。在这里，作者表明，因子XII在多发性硬化症患者的血液中升高，通过CD 87和cAMP激活树突状细胞，并且其阻断抑制了该疾病小鼠模型的免疫病理学。
Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. Factor XII initiates the intrinsic blood coagulation cascade and the kinin system. Here the authors show that Factor XII is elevated in the blood of multiple sclerosis patients, activates dendritic cells via CD87 and cAMP, and its blockade inhibits immunopathology in a mouse model of the disease.