PaperReading
01
P2X7receptorrestrainspathogenicTfhcellgenerationinsystemiclupuserythematosus
CaterinaE.Faliti,RobertaGualtierotti,ElsaRottoli,etal
JExpMed,
TheP2X7receptorsubtypeisanATP-gatednonselectivecationicchannelcharacterizedbydualgating.TheP2rx7gene,encodingforP2X7,iswidelyexpressed,withthehighestlevelsincellsfromnervousandimmunesystems.IthasbeenreportedthatTfhcellswithdeletionofP2rx7resistedextracellularATP(eATP)–inducedporeopeningandcelldeath.However,itisnotclearwhethereATPmightinfluenceTfhcellsatinflammatorysites,whereitispresentathighconcentrations.Inthispaper,theauthorsfoundthatP2rx7deletionexacerbatedimmunopathologyinpristane-inducedlupusmice.Withtheadministrationofpristane,theP2rx7knockoutmiceshowedenhancedsecretionofself-reactiveantibodiesandabnormalGCreaction.Moreover,theyobservedmorepathogenicTfhandkidney-infiltratingTcellsinP2rx7knockoutmicewiththeadministrationofpristane,andtheseTfhmightcontributetoderegulatedGCreaction.Mechanistically,P2X7stimulationpromotedcaspase-mediatedpyroptosisofTfhcellsandcontrolledthedevelopmentofpathogenicICOS+IFN-γ–secretingcells.Notably,circulatingTfhcellsfrompatientswithSLEwerealmostinsensitivetoP2X7-mediatedcontrol,suggestingthatimpairedP2X7activityselectivelycontributestotheimmunopathogenesisofSLE.Inconclusion,theirstudysuggestedthattheP2X7receptormightbeacheckpointregulatorofTfhcellsandanoveltreatmenttargetofSLE.
