Kerstin Göbel, Susann Pankratz, Chloi-Magdalini Asaridou, Alexander M. Herrmann, Stefan Bittner, Monika Merker, Tobias Ruck, Sarah Glumm, Friederike Langhauser, Peter Kraft, Thorsten F. Krug, Johanna Breuer, Martin Herold, Catharina C. Gross, Denise Beckmann, Adelheid Korb-Pap, Michael K. Schuhmann, Stefanie Kuerten, Ioannis Mitroulis, Clemens Ruppert, Marc W. Nolte, Con Panousis, Luisa Klotz, Beate Kehrel, Thomas Korn, Harald F. Langer, Thomas Pap, Bernhard Nieswandt, Heinz Wiendl, Triantafyllos Chavakis, Christoph Kleinschnitz, Sven G. Meuth

• 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 lessAberrant 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.…