TheCD40receptorwasfirstassociatedwithexpressioninBcellsandtheroleitplaysthroughitsligandCD40L(CD154)inmoderatingTcellactivation.BroaderexpressionmayindicateabroaderroleforCD40andCD40LinimmunefunctionanddiseasestatessuchastransplantrejectionandHIVinfection.DisruptionofCD40interactionwithCD40Lmayprovetherapeuticinthetreatmentofautoimmunedisordersorheartdiseaseandmodulationoftheinteractionmayinthefuturebeexploitedincancertreatment.AsamemberoftheTNFreceptorfamily,CD40reliesoninteractionwithTRAFproteinstomediateanintracellularsignalinresponsetoCD40Lbinding.ThepathwaydownstreamofTRAFsactivatesthetranscriptionfactorNF-kappaBthroughakinasepathwayinvolvingmapkinases,NIK(NF-kappaBinducingkinase)andI-kappaBkinases.SomeCD40responseslikeregulationofimmunoglobulinexpressionmightbemediatedbyNF-kappaBtranscriptionalactivation.

Contributor:GlennCrosten,PhD.

REFERENCES:YoungLS.,etal.CD40andepithelialcells:acrossthegreatdivide.ImmunolToday1998Nov;19(11):502-06

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