Th17 cells and Tregs: unlikely allies

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

关键词: Foxp3;    IL‐;    17;    TNF;    TNFR2;    immunosuppression;    inflammation;   

DOI  :  10.1189/jlb.1213633

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

IdentificationofCD4+Foxp3+TregsandTh17modifiedthehistoricalTh1–Th2paradigm.Currently,theTh17–Tregsdichotomyprovidesadominantconceptualframeworkforthecomprehensionofimmunity/inflammationandtolerance/immunosuppressioninanincreasingnumberofdiseases.TargetingproinflammatoryTh17cellsorimmunosuppressiveTregshasbeenwidelyconsideredasapromisingtherapeuticstrategyinthetreatmentofmajorhumandiseases,includingautoimmunityandcancer.TheefficacyandsafetyofsuchtherapyrelyonathoroughunderstandingofimmunobiologyandinteractionofthesetwosubsetsofThcells.Inthisarticle,wereviewrecentprogressconcerningcomplicatedinterplayofTh17cellsandTregs.ThereiscompellingevidencethatTregspotentlyinhibitTh1andTh2responses;however,theinhibitoryeffectofTregsonTh17responsesisacontroversialsubject.ThereisincreasingevidenceshowingthatTregsactuallypromotethedifferentiationofTh17cellsinvitroandinvivoandconsequently,enhancedthefunctionalconsequencesofTh17cells,includingtheprotectiveeffectinhostdefense,aswellasdetrimentaleffectininflammationandinthesupportoftumorgrowth.Ontheotherhand,Th17cellswerealsothemostpotentThsubsetinthestimulationandsupportofexpansionandphenotypicstabilityofTregsinvivo.TheseresultsindicatethatthesetwosubsetsofThcellsreciprocallystimulateeachother.ThisbidirectionalcrosstalkislargelydependentontheTNF–TNFR2pathway.ThesemutualstimulatoryeffectsshouldbeconsideredindevisingfutureTh17cell‐andTreg‐targetingtherapy...

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