Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells
نویسندگان
چکیده
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.
منابع مشابه
O11: Novel Approaches to Prevent Neuroinflammation by Targeting the Coagulation System
There is growing appreciation that other factors not traditionally considered components of the immune system foster inflammation in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). The blood coagulation initiating factor XII was introduced as key mediator of central nervous system (CNS) autoimmunity by modulation of adaptive immune response. Moreov...
متن کاملتمایز سلول‌های دندریتیک مشتق از مونوسیت بر روی لایه‌ای از سلول‌های اندوتلیال به‌عنوان لایه تغذیه‌کننده
Background: The innate and adaptive immune responses are dependent on the migration of leukocytes across endothelial cells. Dendritic cells (DCs) play an important role in the initiation of cellular immune responses during their migration from tissues into the lymph nodes where they interact with endothelial cells of lymphatic vessels. We investigated the effect...
متن کاملThe polyphosphate-factor XII pathway drives coagulation in prostate cancer-associated thrombosis.
Cancer is a leading cause of thrombosis. We identify a new procoagulant mechanism that contributes to thromboembolism in prostate cancer and allows for safe anticoagulation therapy development. Prostate cancer-mediated procoagulant activity was reduced in plasma in the absence of factor XII or its substrate of the intrinsic coagulation pathway factor XI. Prostate cancer cells and secreted prost...
متن کاملO 6: Kininogen Deficiency Ameliorates Neuroinflammation by Reducing Immune Cell Trafficking
Enhanced immune cell trafficking into the central nervous system (CNS) and disruption of the blood brain barrier are pathophysiological hallmarks of neuroinflammatory disorders like multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, recent studies suggest that the coagulation and the contact-kinin system might also be involved in MS developme...
متن کاملتولید سلول های دندریتیک مهاری و سلول های شبه ماکروفاژی با استفاده ترکیبی از فاکتورهای بلوغ
Background and purpose: As professional antigen- presenting cells, dendritic cells are a bridge between innate and adaptive immunity by stimulating T lymphocytes. Recent research has demonstrated the extra ability of the myeloid cells plasticity into different cells in response to environmental stimuli. In the present study, the effect of using combination maturation factors (MCM, TNF-α, poly (...
متن کامل