Immunosuppressive CD11b+Ly6Chi monocytes in pristane‐induced lupus mouse model

[摘要] Myeloid‐derivedsuppressorcellswithimmunosuppressivefunctionshavebeendescribedtobeassociatedwithoneofthemechanismsbywhichmalignanttumorsescapeimmunesurveillance.However,littleisknownabouttheroleofmyeloid‐derivedsuppressorcellsinautoimmunity.Inthecurrentstudy,whenweattemptedtocharacterizetheperitonealcellsinpristane‐inducedlupusmodel,asreportedpreviously,weobservedthatthereweremarkedlyincreasedCD11b+Ly6Chimonocytes.Surprisingly,thistypeofmonocyteswasalmostphenotypicallyidenticaltothereportedmonocyticmyeloid‐derivedsuppressorcells.FurtheranalysisonhowtheseCD11b+Ly6ChicellsaffectedTcellresponseshowedthattheystronglysuppressedTcellproliferationinvitroinamannerdependentoncell–cellcontact,NO,andPGE2.Inaddition,wefoundthatCD11b+Ly6ChimonocytesinhibitedTh1differentiationbutenhanceddevelopmentofforkheadboxp3+CD4+regulatoryTcells.Consistentwiththeinvitroexperimentalresults,theinvivoadoptivecelltransferstudyshowedthatinfusionofpristane‐treatedsyngeneicCD11b+Ly6Chimonocytessignificantlysuppressedtheproductionofanti‐keyholelimpethemocyaninantibodiesinducedbykeyholelimpethemocyaninimmunization.Inaddition,wefoundthatCD11b+Ly6Chimonocyteswerealsoincreasedsignificantlyinspleenandperipheralbloodandshowedimmunosuppressivecharacteristicssimilartotheirperitonealcounterparts.OurfindingsindicatethatCD11b+Ly6Chimonocytesinapristane‐inducedlupusmousemodelaremonocyticmyeloid‐derivedsuppressorcellsinsteadofinflammatorymonocytes,asdemonstratedpreviously.Toourknowledge,thisisthefirsttodescribemyeloid‐derivedsuppressorcellsinapristane‐inducedlupusmousemodel,whichmayleadtoabetterunderstandingoftheroleofCD11b+Ly6Chimonocytesinthisspecificpristane‐inducedlupusmodel...

[学科分类] 生理学

[关键词] myeloid‐derived suppressor cell;regulatory T cell;prostaglandin E2;nitric oxide synthase;IL‐10