Regulation of Interferon‐γ During Innate and Adaptive Immune Responses

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1、CHAPTER2RegulationofInterferon-gDuringInnateandAdaptiveImmuneResponses†JamieR.Schoenborn*andChristopherB.WilsonContents1.Introduction432.IFN-g-ProducingCells452.1.NKcells452.2.NKTcells452.3.CD8Tcells462.4.CD4Tcellsplaymultiplerolesinadaptiveimmunity463.SignalingPathwaysControllingIFN

2、-gProductionbyNKCells483.1.NKreceptorsprovideadynamicrheostattocontrolNKcellresponses483.2.IL-12isapotentactivatorofIFN-gproductioninNKcells493.3.IL-15andIL-2regulateNKcelldevelopmentandcontributetoIFN-gproduction513.4.TGF-bisanegativeregulatorofIFN-gproductionandNKcelldevelopment514

3、.ControlofIFN-gProductionbyNKTCells525.SignalingPathwaysintheDifferentiationofCD4andCD8TCells535.1.NaiveTcellsrequireantigenstimulationforproliferationandeffectorcommitment535.2.TcellsrequirecytokinesignalsforsustainedIFN-gexpression54*MolecularandCellularBiologyGraduateProgram,Unive

4、rsityofWashington,Seattle,Washington{DepartmentofImmunology,UniversityofWashington,Seattle,WashingtonAdvancesinImmunology,Volume96#2007ElsevierInc.ISSN0065-2776,DOI:10.1016/S0065-2776(07)96002-2Allrightsreserved.4142JamieR.SchoenbornandChristopherB.Wilson5.3.OtherfactorsinfluencingTh

5、1lineagecommitment575.4.TGF-bandIL-6negativelyregulateIFN-gproductionandTh1development585.5.IFN-gproductionbymemoryTcellsinresponsetocytokinestimulation596.TranscriptionFactorsDownstreamoftheTCR,ActivatingNKReceptors,andCytokineReceptors606.1.FactorsdownstreamoftheTCR,costimulatory,a

6、ndactivatingNKreceptors606.2.STATsareactivatedinresponsetocytokinereceptorsignaling686.3.T-boxfamilymembersarecrucialforIFN-gsecretion707.EpigeneticProcessesGovernPlasticityofCellFateChoicesandHelptoIdentifyDistalRegulatoryElements728.TranscriptionalRegulatoryElementsWithintheIfngGen

7、e748.1.RegulatoryelementswithintheIfngpromoterandgene748.2.IdentificationofcandidatedistalregulatoryelementsintheIfnglocus779.FunctionalAnalysisofCandidateDistalRegulatoryElementsintheIfngLocus8210.ConclusionsandFutureDirections84Acknowledgments85References85AbstractInterferon-g(IFN-

8、g)iscrucialf