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

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

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

DOI  :  10.1189/jlb.3A0415-158R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 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...

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