Blood Coagulation Factor XII Drives Adaptive Immunity During Neuroinflammation Via CD87-mediated Modulation of Dendritic Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2016 May 19

PMID 27188843

Citations 66

Authors

Kerstin Gobel

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

Affiliations

Soon will be listed here.

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.

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