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Nat Commun. 2016 May 18;7:11626. doi: 10.1038/ncomms11626.

Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells.

Author information

1
Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
2
Department of Neurology, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, Germany.
3
Department of Neurology, University Hospital Würzburg, 97080 Würzburg, Germany.
4
Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, 48149 Münster, Germany.
5
Department of Anatomy and Cell Biology, University of Würzburg, 97070 Würzburg, Germany.
6
Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, University Clinic Carl Gustav Carus, Technische Universität of Dresden, 01307 Dresden, Germany.
7
Department of Internal Medicine, Universities of Giessen &Marburg Lung Center (UGMLC)/Member of the German Center for Lung Research (DZL), Justus-Liebig University, 35392 Giessen, Germany.
8
CSL Behring GmbH, 35041 Marburg, Germany.
9
CSL Limited, Bio21 Institute, Parkville, Victoria 3010, Australia.
10
Department of Anesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Hemostasis, University of Münster, 48149 Münster, Germany.
11
Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
12
Department of Cardiology and Cardiovascular Medicine, Section for Cardioimmunology, University Clinic of Tübingen, 72076 Tübingen, Germany.
13
Rudolf Virchow Center, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, University of Würzburg, 97080 Würzburg, Germany.
14
Department of Neurology, University Hospital Essen, 45147 Essen, Germany.

Abstract

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.

PMID:
27188843
PMCID:
PMC4873982
DOI:
10.1038/ncomms11626
[Indexed for MEDLINE]
Free PMC Article

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