The role and potential therapeutic application of myeloid‐derived suppressor cells in TNBS‐induced colitis

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

关键词: inflammatory bowel disease;    cell‐;    based immunotherapy;    immune down‐;    regulation;    murine colitis;   

DOI  :  10.1189/jlb.0113050

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

MDSCs,aheterogeneouspopulationofcellsthatexpandduringmanypathogenicconditions,haveremarkableabilitiestosuppressTcellresponses.Theirroleinmurinecolitis,inducedbyTNBSandtherapeuticapplication,remainsunclear.MurinecolitiswasinducedthroughintrarectallyadministratingTNBS,twice.MDSCsinspleenandcolonicLPMCswereidentifiedusingflowcytometricanalysis.Inadoptivetransfer,MDSCswereisolatedfromspleenafterTNBSchallengesbyusingmicrobeadsorgeneratedinvitrobycoculturingbonemarrowcellswithHSCsandthentransferredintonaïvemice.Twohourslater,micewerethenchallengedwithTNBS,once/weekfor2weeks.ThemicewerekilledfourdaysafterthesecondTNBSdelivery,andintestinalinflammationandcytokinelevelsandMDSCpercentageswereevaluated.ThepercentagesofCD11b+Gr‐1+MDSCsandsubsets(CD11b+Ly6C+andCD11b+Ly6G+MDSCs)wereincreasedinspleenand/orcolonicLPMCsincolitismiceandalsocorrelatedwiththeseverityofintestinalinflammation.MDSCsisolatedfromcolitismicesuppressedtheproliferationofsplenocytesinvitro.AdoptivetransferofMDSCs,isolatedfromcolitismiceorgeneratedinvitro,decreasedintestinalinflammation,levelsofIFN‐γ,IL‐17,andTNF,andpercentagesofspleenMDSCswhencomparedwithcontrols.MDSCsthathaveinhibitoryfunctioninvitroandinvivoareincreasedandcorrelatedwithintestinalinflammation,suggestingthattheymaybeusedasabiomarkerofdiseaseactivityandacell‐basedbiotherapyinIBD...

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