6533b856fe1ef96bd12b1c8e
RESEARCH PRODUCT
Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells
Catharina C. GrossThomas PapThomas KornChristoph KleinschnitzTobias RuckClemens RuppertDenise BeckmannJohanna BreuerSarah GlummSusann PankratzStefanie KuertenIoannis MitroulisStefan BittnerStefan BittnerHarald F. LangerKerstin GöbelBernhard NieswandtPeter KraftCon PanousisMartin HeroldAdelheid Korb-papSven G. MeuthThorsten F. KrugLuisa KlotzMichael K. SchuhmannMonika MerkerChloi-magdalini AsaridouBeate E. KehrelHeinz WiendlMarc W. NolteTriantafyllos ChavakisAlexander M. HerrmannFriederike Langhausersubject
AdultMale0301 basic medicineEncephalomyelitis Autoimmune ExperimentalMultiple Sclerosisanimal structuresT-LymphocytesScienceMedizinGeneral Physics and AstronomyKininsCoagulation Factor XIIAdaptive ImmunityBiologymedicine.disease_causeArticleGeneral Biochemistry Genetics and Molecular BiologyReceptors Urokinase Plasminogen ActivatorAutoimmunityYoung Adult03 medical and health sciencesImmune systemddc:570medicineAnimalsHumansddc:610cardiovascular diseasesNeuroinflammationAgedFactor XIIMultidisciplinaryInterleukin-17QExperimental autoimmune encephalomyelitisCell DifferentiationDendritic CellsGeneral ChemistryMiddle Agedmedicine.diseaseAcquired immune systemMice Inbred C57BL030104 developmental biologyNeuroimmunologyFactor XIIImmunologyFemaleKallikreinscirculatory and respiratory physiologydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-05-01 | Nature Communications |