Intestinal epithelial cell‐derived integrin αβ6 plays an important role in the induction of regulatory T cells and inhibits an antigen‐specific Th2 response

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

关键词: tolerogenic dendritic cell;    epithelium;    transforming growth factor‐;    β;    T lymphocyte;    allergy;    oral tolerance;   

DOI  :  10.1189/jlb.1210696

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TolerogenicDCsandTregsarebelievedtoplayacriticalroleinoraltolerance.However,themechanismsofthegenerationoftolerogenicDCsandactivationofTregsinthegutremainpoorlyunderstood.ThisstudyaimstodissectthemolecularmechanismsbywhichIECsandproteinantigeninducefunctionaltolerogenicDCsandTregs.Expressionofαvβ6bygutepithelialcell‐derivedexosomes,itscouplingwithfoodantigen,andtheirrelationshipwiththedevelopmentoffunctionaltolerogenicDCsandTregswereexaminedbyusinginvitroandinvivoapproaches.TheresultsshowthatIECsup‐regulatedtheintegrinαvβ6uponuptakeofantigens.Theepithelialcell‐derivedexosomesentrappedandtransportedαvβ6andantigenstotheextracellularenvironment.TheuptakeofantigensaloneinducedDCstoproduceLTGFβ,whereasexosomescarryingαvβ6/antigenresultedintheproductionofabundant,activeTGF‐βinDCsthatconferredtoDCsthetolerogenicproperties.Furthermore,αvβ6/OVA‐carrying,exosome‐primedDCswerefoundtopromotetheproductionofactiveTGF‐βinTregs.Thus,invivoadministrationofαvβ6/OVA‐ladenexosomesinducedthegenerationofTregsandsuppressedskewedTh2responsestowardfoodantigenintheintestine.OurstudyprovidesimportantmolecularinsightsintothemolecularmechanismsofTregdevelopmentbydemonstratinganimportantroleofIEC‐derivedexosomescarryingαvβ6andfoodantigenintheinductionoftolerogenicDCsandantigen‐specificTregs...

【 授权许可】

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