Oral administration of carbonic anhydrase I ameliorates murine experimental colitis induced by Foxp3−CD4+CD25− T cells

[摘要] IBDsarethoughttoinvolveuncontrolledinnateandadaptiveimmunityagainstintestinalself‐antigensandbacterialantigens.MouseCAIisamajorcecalbacterialantigeninfecalextractsandisimplicatedinthepathogenesisofIBD.WeshowherethatoraltolerizationtoCAIinducedantigen‐specificprotectionfromintestinalinflammationinamurinemodel.OraladministrationofCAIbutnotirrelevantantigen(KLH)amelioratedCD4+CD25−TcelltransfermurinecolitisandDSS‐inducedmurinecolitis.Next,weinvestigatedthemechanismsinvolvedinthetherapeuticeffectsoforaladministration,suchasinductionofALDH1a2,transcriptionfactors,cytokines,CD103+CD11c+DCs,andgenerationofTregs.OraladministrationofCAIinducedALDH1a2mRNAexpressionintheMLNandcolon.WhencomparedwithPBS‐treatedmice,CAI‐treatedmicehadhigherFoxp3+CD4+CD25+TregandCD103+CD11c+DCnumbersintheMLNandcolon;hadhigherTGF‐βproductionintheMLNandcolon;hadlowerRORγtmRNAexpressionintheMLNandcolon;andhadlowerIL‐17mRNAexpressionandproductionintheMLN.TheseresultsdemonstratethatoraladministrationofCAIinducedantigen‐specificimmunetolerancebygeneratingFoxp3+CD4+CD25+TregsandinhibitingTh17cellsinamurinecolitismodel,thussuggestingthatoraltolerizationwithCAIisaneffectivetherapeuticstrategyforIBDregulation...

[学科分类] 生理学

[关键词] tolerance;inflammatory bowel disease;aldehyde dehydrogenase family 1a2;regulatory T cell;CD103+ dendritic cell