Reciprocal regulation of CXCR4 and CXCR7 in intestinal mucosal homeostasis and inflammatory bowel disease

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

关键词: Crohnˈ;    s disease;    ulcerative colitis;    chemokines;    CXCL12;   

DOI  :  10.1189/jlb.0111101

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

IBDsarecharacterizedbyincreasedinfluxofimmunecellstothemucosaofgeneticallysusceptiblepersons.Cellularmigrationtoinjurysitesismediatedbychemokines.CXCL12isaubiquitous,constitutivechemokinethatparticipatesinstemcellproliferationandmigrationandmediatesTlymphocytemigrationtoinflamedtissues.WehaverecentlyreportedthatCXCL12anditsreceptor,CXCR4,areexpressedinnormalandmoreprominently,inflamedhumanintestinalmucosa.However,theinteractionsandrolesofCXCL12anditsreceptors,CXCR4andtherecentlydiscoveredCXCR7,inintestinalinflammationhavenotbeendefined.Inthepresentstudy,wefurtherdissectedtheeffectsofCXCL12onlymphocytesinintestinalhomeostasisandinflammationanddelineatedtheinterplaybetweenCXCL12anditsreceptorsCXCR4andCXCR7.Tothatend,freshmononuclearcellswereisolatedfrommucosaandPBofhealthyorIBDpatients.Phenotypicalandfunctionalassayswereconductedusingflowcytometry,Transwellmigrationchambers,andELISA.ThedatashowthatCXCL12‐mediatedmigrationofTcellsisCXCR4‐butnotCXCR7‐dependent.TcellactivationreciprocallyregulatesCXCR7andCXCR4expressionandmigratorycapacity.IBDPBTsexpressedmoreCXCR7thannormalPBTs.Finally,TcellsattractedbyCXCL12aremostlyofamemoryphenotype.Inconclusion,thepresentstudysuggeststhattheinterplaybetweenCXCL12anditsreceptorsaffectshomeostasisandinflammationintheintestinalmucosa...

【 授权许可】

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