TLR2 deletion promotes arthritis through reduction of IL‐10

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: macrophage;    inflammation;    cytokine;    IgG Fc receptor;    osteoclastogenesis;   

DOI  :  10.1189/jlb.0912473

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

RAisachronicinflammatorydiseasecharacterizedbythepersistentexpressionofinflammatorycytokinesfrommacrophages,whichmaybemediated,inpart,throughTLR2signaling.EarlierstudiesdemonstratearoleforTLR2signalingindampeningthearthritisinIL‐1Ra−/−mice,whichwasmediatedthroughTcells.ThisstudywasperformedtodeterminewhetherTLR2signalingplaysaroleinthepathogenesisofTcell‐independentarthritistriggeredbytransferringserumfromK/BxNmice.WedocumentedmoreseverearthritisinTlr2−/−micecomparedwithWTcontrols.TheTlr2−/−micealsodemonstratedincreasedinflammation,erosion,pannusformation,andosteoclastogenesis,aswellasincreasedIL‐1βanddecreasedIL‐10withinthejoints.Invitrobonemarrow‐differentiatedmacrophagesexpressedcomparablelevelsofactivatingandinhibitoryFcγRs,howeverwhenstimulatedwithimmunecomplexes,theTlr2−/−macrophagesexpresseddecreasedIL‐10andreducedactivationofAktandERK.OurfindingsindicatethatTlr2−/−promotestheeffectorphaseofarthritisthroughdecreasedIL‐10bymacrophages,whichisimportant,notonlyasananti‐inflammatorycytokinebutalsoinrestrainingthedifferentiationandactivationofosteoclasts...

【 授权许可】

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