Requirement of Interaction between Mast Cells and Skin Dendritic Cells to Establish Contact Hypersensitivity 英文参考文献.docVIP

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Requirement of Interaction between Mast Cells and Skin Dendritic Cells to Establish Contact Hypersensitivity 英文参考文献.doc

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Requirement of Interaction between Mast Cells and Skin Dendritic Cells to Establish Contact Hypersensitivity 英文参考文献

RequirementofInteractionbetweenMastCellsandSkin DendriticCellstoEstablishContactHypersensitivity AtsushiOtsuka1,2,MasatoKubo3,TetsuyaHonda1,GyoheiEgawa1,SaekoNakajima1,HideakiTanizaki1, BongjuKim2,SatoshiMatsuoka2,TakeshiWatanabe2,SusumuNakae4,YoshikiMiyachi1 ,Kenji Kabashima1* 1DepartmentofDermatology,KyotoUniversityGraduateSchoolofMedicine,Kyoto,Japan,2CenterforInnovationinImmunoregulativeTechnologyandTherapeutics, KyotoUniversityGraduateSchoolofMedicine,Kyoto,Japan,3LaboratoryforSignalNetwork,ResearchCenterforAllergyandImmunology,RIKENYokohamaInstitute, Tsurumi,Yokohama,Kanagawa,Japan,4FrontierResearchInitiative,InstituteofMedicalScience,UniversityofTokyo,Minato,Tokyo,Japan Abstract Theroleofmastcells(MCs)incontacthypersensitivity(CHS)remainscontroversial.ThisisdueinparttotheuseoftheMC- deficientKit W/Wvmousemodel,sinceKit W/Wvmicecongenitallylackothertypesofcellsasaresultofapointmutationinc- kit.Arecentstudyindicatedthattheintronicenhancer(IE)forIl4genetranscriptionisessentialforMCsbutnotinothercell types.Theaimofthisstudyistore-evaluatetherolesofMCsinCHSusingmiceinwhichMCscanbeconditionallyand specificallydepleted.TransgenicMas-TRECKmiceinwhichMCsaredepletedconditionallywerenewlygeneratedusingcell- type specific gene regulation by IE. Using this mouse, CHS and FITC-induced cutaneous DC migration were analyzed. 2+ ChemotaxisassayandcytoplasmicCa imagingwereperformedbyco-cultureofbonemarrow-derivedMCs(BMMCs)and bonemarrow-deriveddendriticcells(BMDCs).InMas-TRECKmice,CHSwasattenuatedwhenMCsweredepletedduringthe sensitizationphase.Inaddition,bothmaturationandmigrationofskinDCswereabrogatedbyMCdepletion.Consistently, BMMCsenhancedmaturationandchemotaxisofBMDCinICAM-1andTNF-adependentmannersFurthermore,stimulated 2+ BMDCsincreased intracellularCa ofMCupondirectinteraction andup-regulated membrane-boundTNF-aonBMMCs. TheseresultssuggestthatMCsenhanceDCfunctionsbyinteractingwithDCsintheskintoestablishthesensitizationphase ofCHS. Citation:OtsukaA,KuboM,HondaT,Eg