Implication of indolamine 2,3 dioxygenase in the tolerance toward fetuses, tumors, and allografts

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

关键词: ;    l‐;    tryptophan catabolism;    pregnancy;    trophoblast;    chronic disease;    autoimmunity;    cell therapy;   

DOI  :  10.1189/jlb.0712347

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

MammalianIDOisaheme‐containingenzymewhosemainactivityinmammalsistodegradetheessentialaminoacidtrypintol‐kynurenine.Althoughthelinkbetweenitsenzymaticactivityandtheimmuneresponseisnotstraightforward,severallinesofevidencesuggestthatthisenzymeisinvolvedinfightinginfectionsandparadoxically,alsointheestablishmentoftheimmunetoleranceassociatedwithfetusimplantationandwiththedevelopmentofoncogenicprocesses.IDOisassociatedwiththesuccessfuldevelopmentofthefetus.Itparticipatesearlyinpregnancytotheefficientinvasionoftheuterinemucosabythenascenttrophoblastandremainsactivethroughoutthewholeprocess,asillustratedbythedecreaseinsystemictrypfromthesecondtrimesterofgestationandthereturntonormalvaluesafterdelivery.Theshort‐termactivationofIDOinresponsetoinvadingpathogensandemergingtumorsparticipatesintheeliminationofthesethreats,whereasthesustainedactivationofIDOoftenresultsinastateofimmunetolerancethatmayfavorchronicinfectionsandtheuncontrolledproliferationofmalignantcells.However,despitethesepotentialdeleteriouseffectsofIDO,theenzymeisinstrumentalinmaintainingtheperipheraltolerancethatisrequiredtoavoidautoimmunediseases.Below,wereviewtheimplicationofIDOactivationuponthephysiologicaldevelopmentofthefetusandthepathologicaldevelopmentoftumorsanddiscusswhethersuchanenzymecouldbeusedasatherapeutictooltodecreasetherateofallograftrejectionsviaitspotentimmunomodulatoryproperties...

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