WASp‐dependent actin cytoskeleton stability at the dendritic cell immunological synapse is required for extensive, functional T cell contacts

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

关键词: DC;    ICAM‐;    1;    podosomes;    FRAP;    Arp2/3;   

DOI  :  10.1189/jlb.2A0215-050RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Theimmunologicalsynapseisahighlystructuredandmolecularlydynamicinterfacebetweencommunicatingimmunecells.AlthoughtheimmunologicalsynapsepromotesTcellactivationbydendriticcells,thespecificorganizationoftheimmunologicalsynapseonthedendriticcellsideinresponsetoTcellengagementislargelyunknown.Inthisstudy,confocalandelectronmicroscopytechniqueswereusedtoinvestigatetheroleofdendriticcellactinregulationinimmunologicalsynapseformation,stabilization,andfunction.Inthedendriticcell‐restrictedabsenceoftheWiskott‐Aldrichsyndromeprotein,animportantregulatoroftheactincytoskeletoninhematopoieticcells,theimmunologicalsynapsecontactwithTcellsoccupiedasignificantlyreducedsurfacearea.Atamolecularlevel,theactinnetworklocalizedtotheimmunologicalsynapseexhibitedreducedstability,inparticular,oftheactin‐relatedprotein‐2/3‐dependent,short‐filamentnetwork.Thiswasassociatedwithdecreasedpolarizationofdendriticcell‐associatedICAM‐1andMHCclassII,whichwaspartiallydependentonWiskott‐Aldrichsyndromeproteinphosphorylation.Withtheuseofsupportedplanarlipidbilayersincorporatinganti‐ICAM‐1andanti‐MHCclassIIantibodies,thedendriticcellactincytoskeletonorganizedintorecognizablesynapticstructuresbutinterestingly,formedWiskott‐Aldrichsyndromeprotein‐dependentpodosomeswithinthisarea.Thesefindingsdemonstratethatintrinsicdendriticcellcytoskeletalremodelingisakeyregulatorycomponentofnormalimmunologicalsynapseformation,likelythroughconsolidationofadhesiveinteractionandmodulationofimmunologicalsynapsestability...

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