The Src kinase Fyn is protective in acute chemical‐induced colitis and promotes recovery from disease

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

关键词: inflammatory bowel disease;    Foxp3;    regulatory T cell;    dextran sodium sulfate;   

DOI  :  10.1189/jlb.3A0814-405RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Despiteprogressinunderstandingentericinflammation,currenttherapies,althougheffectiveinmanypatientswithinflammatoryboweldisease(IBD),havesignificantside‐effects,and,inmanypatients,itisrefractorytotreatment.TheSrckinaseFynmediatedIFN‐γ‐inducedincreasedpermeabilityinmodelepithelia,andsowehypothesizedthatinhibitionofFynkinasewouldbeanti‐colitic.Mice[B6.129SF2/Jwild‐type(WT),FynKO,orchimeras]received2.5%dextransodiumsulfate(DSS)ornormalwaterfor10dandwerenecropsiedimmediatelyor3dlater.GutpermeabilitywasassessedbyFITC‐dextranflux,colitisbymacroscopicandhistologicparameters,andimmunecellstatusbycytokineproductionandCD4+TcellFoxp3expression.FynKOmiceconsistentlydisplayedsignificantlyworseDSS‐induceddiseasethanWT,correlatingwithdecreasedIL‐10andincreasedIL‐17insplenocytesandthegut;FynKOmicefailedtothriveafterremovaloftheDSSwater.AnalysisofchimericmiceindicatedthattheincreasedsensitivitytoDSSwasduetothelackofFynkinaseinhematopoietic,butnotstromal,cells,inaccordancewithFyn+TcellincreasesinWTmiceexposedtoDSSandFynKOmicehavingareducednumberofCD4+Foxp3+cellsinbaselineorcoliticconditionsandareducedcapacitytoinduceFoxp3expressioninvitro.OtherexperimentssuggestthatthecolonicmicrobiotainFynKOmiceisnotpreferentiallycolitogenic.Contrarytoourexpectation,theabsenceofFynkinaseresultedingreaterDSS‐induceddisease,andanalysisofchimericmiceindicatedthatleukocyteFynkinaseisbeneficialinlimitingcolitis...

【 授权许可】

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