title: Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells.
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.
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Göbel
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Pankratz
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Chloi-Magdalini
authors.initials: CM
authors.lastname: Asaridou
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Herrmann
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.|Department of Neurology, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bittner
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Merker
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ruck
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Glumm
authors.affiliation: Department of Neurology, University Hospital Würzburg, 97080 Würzburg, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Langhauser
authors.affiliation: Department of Neurology, University Hospital Würzburg, 97080 Würzburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Thorsten F
authors.initials: TF
authors.lastname: Krug
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Breuer
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Herold
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Catharina C
authors.initials: CC
authors.lastname: Gross
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, 48149 Münster, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Beckmann
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, 48149 Münster, Germany.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Korb-Pap
authors.affiliation: Department of Neurology, University Hospital Würzburg, 97080 Würzburg, Germany.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Schuhmann
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, 97070 Würzburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuerten
authors.affiliation: Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, University Clinic Carl Gustav Carus, Technische Universität of Dresden, 01307 Dresden, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mitroulis
authors.affiliation: 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.
authors.forename: Clemens
authors.initials: C
authors.lastname: Ruppert
authors.affiliation: CSL Behring GmbH, 35041 Marburg, Germany.
authors.forename: Marc W
authors.initials: MW
authors.lastname: Nolte
authors.affiliation: CSL Limited, Bio21 Institute, Parkville, Victoria 3010, Australia.
authors.forename: Con
authors.initials: C
authors.lastname: Panousis
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Luisa
authors.initials: L
authors.lastname: Klotz
authors.affiliation: Department of Anesthesiology, Intensive Care and Pain Medicine, Experimental and Clinical Hemostasis, University of Münster, 48149 Münster, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Kehrel
authors.affiliation: Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Korn
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, Section for Cardioimmunology, University Clinic of Tübingen, 72076 Tübingen, Germany.
authors.forename: Harald F
authors.initials: HF
authors.lastname: Langer
authors.affiliation: Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, 48149 Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pap
authors.affiliation: Rudolf Virchow Center, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, University of Würzburg, 97080 Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Department of Clinical Pathobiochemistry and Institute for Clinical Chemistry and Laboratory Medicine, University Clinic Carl Gustav Carus, Technische Universität of Dresden, 01307 Dresden, Germany.
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.affiliation: Department of Neurology, University Hospital Würzburg, 97080 Würzburg, Germany.|Department of Neurology, University Hospital Essen, 45147 Essen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.affiliation: Department of Neurology, Clinic of Neurology and Institute for Translational Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000368:Aged; D000818:Animals; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005174:Factor XII / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D007610:Kallikreins / Q000378:metabolism; D007705:Kinins / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D055815:Young Adult
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17; D007705:Kinins; C524899:Plaur protein, mouse; D055293:Receptors, Urokinase Plasminogen Activator; D005174:Factor XII; D007610:Kallikreins