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

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

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

DOI  :  10.1189/jlb.1212612

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 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...

【 授权许可】

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