grant
CD8 T cell derived Granzyme K activates complement that drives synovial fibroblast inflammation
Organization BRIGHAM AND WOMEN'S HOSPITALLocation BOSTON, UNITED STATESPosted 22 Sept 2023Deadline 31 Aug 2028
NIHUS FederalResearch GrantFY2025(TNF)-αAddressAffectAffinityAnaphylatoxinsApoptosisApoptosis PathwayArthritisAtrophic ArthritisAutomobile DrivingBindingBlood SerumBlood leukocyteBody TissuesC 1 EsteraseC 2aC 3 ConvertaseC 5b-9C1 EsteraseC1 sC1sC2aC3 ActivatorC3 ConvertaseC3 aC3 convertase activatorC3-C5 ConvertaseC3PA ConvertaseC3PAseC3aC3bC4 bC4bC5 Cleaving EnzymeC5 ConvertaseC5 aC5aC5bC5b-9CD4 CellsCD4 Positive T LymphocytesCD4 T cellsCD4 helper T cellCD4 lymphocyteCD4+ T-LymphocyteCD4-Positive LymphocytesCD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCRISPRCRISPR/Cas systemCachectinCartilageCartilaginous TissueCaspaseCaspase GeneCell BodyCell DegranulationCell membraneCell surfaceCell-Death ProteaseCell-Mediated Lympholytic CellsCellsChargeChronicClustered Regularly Interspaced Short Palindromic RepeatsCollagen ArthritisCollagen-Induced ArthritisComplementComplement 1 EsteraseComplement 1sComplement 3 ConvertaseComplement 3aComplement 3bComplement 4bComplement 5 ConvertaseComplement 5aComplement ActivationComplement C 5bComplement C3aComplement C3bComplement C4bComplement C5aComplement Complex C5b-9Complement Factor DComplement Membrane Attack ComplexComplement Protein DComplement ProteinsComplement ReceptorComplement component C1sCysteine EndopeptidasesCysteine ProteaseCysteine ProteinasesCytolytic T-CellCytolytic Terminal Complement ComplexCytoplasmic MembraneCytotoxic T CellCytotoxic T-LymphocytesD component of complementDepositDepositionDiarthrosisDiseaseDisorderEAC 423EAC142ElectrostaticsElementsFK506 Binding Protein 12-Rapamycin Associated Protein 1FKBP12 Rapamycin Complex Associated Protein 1FRAP1FRAP1 geneFRAP2Factor DFibroblastsGBGaseGenerationsGlycosaminoglycansGranzymeHumanICE-like proteaseInflammationInflammatoryInflammatory ArthritisJointsLectinLeukocytesLeukocytes Reticuloendothelial SystemLifelong disabilityLymphatic cellLymphocyteLymphocyticMAP19MASP2MASP2 geneMacrophage-Derived TNFMannan-Binding Lectin Serine Protease 2Marrow Mast CellMarrow leukocyteMechanistic Target of RapamycinMediatingMembrana Synovialis Capsulae ArticularisMembraneMembrane Attack ComplexMetabolicMetabolic ActivationMiceMice MammalsModelingModern ManMolecular InteractionMonocyte-Derived TNFMucopolysaccharidesMurineMusOrganoidsPathologyPathway interactionsPermanent disabilityPlasma MembranePlayProactivator ConvertaseProcessProductionProgrammed Cell DeathProperdin Factor DProtein SecretionProteinsPublishingRAFT1Recombinant C5aRecombinantsResearchRheumatoid ArthritisRoleSerine EndopeptidasesSerine ProteaseSerine Protein HydrolasesSerine ProteinasesSerumSourceSurfaceSynovial MembraneSynovial jointSynovitisSynoviumT-Cell SubsetsT-CellsT-LymphocyteT-Lymphocyte SubsetsT4 CellsT4 LymphocytesT8 CellsT8 LymphocytesTNFTNF ATNF AlphaTNF geneTNF-αTNFATNFαTerminal Complement ComplexTestingTissue BasophilsTissuesTumor Necrosis FactorTumor Necrosis Factor-alphaWhite Blood CellsWhite CellWorkadipocyte 28 kDa proteinadipsinarthriticbonecell typecomplement 2acomplement 5bcomplement C2acomplement C2a fragmentcomplement C5bcomplement pathwaycomplement pathway regulationcomplementationcystein proteasecystein proteinasecysteine endopeptidasedrivingdrug developmentimmunopathologyin vivoinflamed jointinflamed synovial tissueinflamed synoviuminsightjoint damagejoint inflammationjoint injuryjoint swellingjoint traumakiller T celllymph cellmTORmammalian target of rapamycinmast cellmastocytemembrane structuremouse modelmurine modelnew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetpathwayplasmalemmaresponserheumatic arthritissocial rolesynovial inflammationthymus derived lymphocytewhite blood cellwhite blood corpuscle
Description preview
The role of T cells in RA is established, but nearly all research has focused on CD4 T cells. We have
shown that CD8 T cells are similarly expanded and activated in inflamed RA synovium yet do not belong to the
typical granzyme (Gzm) B+ cytotoxic T lymphocyte (CTL) subset. Instead, they express high levels of GzmK
whose function is not well…
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