Folate receptor‐β constitutes a marker for human proinflammatory monocytes

[摘要] ActivatedmacrophagesarecommonlyinvolvedinthepathogenesisofinflammatoryandautoimmunediseasesandhavebeenfrequentlyreportedtooverexpressFR‐β.AlthoughFR‐targetedtherapiesaimedateliminatingactivatedmacrophageshaveshownpromisefortreatinginflammatorydiseases,littleworkhasbeenperformedtoevaluatewhetherotherhematopoieticcellsmightalsoexpressFR‐β.AnalysisofperipheralbloodcellswithamAbtohumanFR‐βrevealsthatonlymonocytesexpressFR‐β.Molecularcharacterizationofthesecirculatingmonocytesfurtherdemonstratesthatsolelytheclassic/proinflammatorysubset(CD14highCD16−)expressestheFRandthatonlyCD14highCD16−FR‐β+monocytesalsodisplaytheabilitytobindfolate‐linkedmolecules.ConfirmationthatthissubsetofmonocytesindeedconstitutestheproinflammatorysubpopulationwasobtainedbydemonstratingcoexpressionofFR‐βwithotherproinflammatorymarkers,includingCCR2andHLA‐DR.SynovialmonocytesfromthejointsofpatientswithRAwerealsoshowntoexpressFR‐β.Asinhibitionofthechemotaxisofproinflammatorymonocytesintositesofinflammationhasbeenexploredfrequentlyasameansofcontrollingautoimmunediseases,demonstrationthatFR‐βisuniquelyexpressedonthisproinflammatorysubpopulationoffersanewstrategytosuppressmigrationofinflammatorymonocytesintositesofinflammation...

[学科分类] 生理学

[关键词] inflammatory subset;folate targeting;immunotherapy;inflammation