Dendritic cell expression of ADAM23 governs T cell proliferation and cytokine production through the α(v)β(3) integrin receptor

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

关键词: disintegrin;    adhesion;    antigen presentation;    cytoskeleton;    costimulation;   

DOI  :  10.1189/jlb.2HI1115-525R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ADAM23isamemberofthebrainmacrophage‐derivedchemokinefamily.StructuralhomologyofADAMproteinssuggeststheirfunctionasintegrinreceptors.PreviousstudieshavelinkedADAM23asadominantcontributortobraindevelopmentandcancermetastasis.ThepresentstudiesnowshowthatADAM23expressiononDCspartiallygovernsantigen‐presentationcapacitiestoresponderCD4+Tcells.WiththeuseofRNAiapproaches,knockdownofADAM23inmurineBMDCsresultedinimpairedTcellactivation,proliferation,andcytokineproduction.KnockdowndidnotalterthematurationprofileofDCs(i.e.,costimulatorymoleculeexpressionorproductionofproinflammatorycytokines)butmarkedlyimpairedcognateTcellresponses.Therewasasignificantdecreaseinantigen‐specificclonalexpansioncoupledwithaglobaldecreaseinThcytokineproduction.Impairedearlyactivationandproliferationdidnotalter/skewthebalanceofThpolarizationbutsignificantlydepressedtotallevelsofIL‐2,IFN‐γ,IL‐4,andIL‐17cytokineproductioninCD4+TcellsprimedbyADAM23knockdownversuscontrolDCs.Finally,neutralizingantibodiestargetingtheα(v)β(3)integrinreceptorsresultedinsimilarphenotypesofimpairedCD4+Tcellresponses.Takentogether,thesestudiesshowanovelroleofADAM23ingoverningDCantigenpresentationtocognateCD4+Tcells...

【 授权许可】

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