Th17 cells and Tregs: unlikely allies

[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...

[学科分类] 生理学

[关键词] Foxp3;IL‐17;TNF;TNFR2;immunosuppression;inflammation