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

Goebel 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 (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 7

Article Number: 11626

DOI: 10.1038/ncomms11626

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 with CRIS profile

Stefanie Kürten

Involved external institutions

Westfälische Wilhelms-Universität (WWU) Münster DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE) Universitätsklinikum Münster DE Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) DE Germany (DE) CSL Behring GmbH DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE) Julius-Maximilians-Universität Würzburg DE Germany (DE) Technische Universität Dresden DE Germany (DE) CSL Limited AU Australia (AU) Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Goebel, K., Pankratz, S., Asaridou, C.-M., Herrmann, A.M., Bittner, S., Merker, M.,... Meuth, S.G. (2016). Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells. Nature Communications, 7. https://doi.org/10.1038/ncomms11626

MLA:

Goebel, Kerstin, et al. "Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells." Nature Communications 7 (2016).

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