The multiple faces of CXCL12 (SDF‐1α) in the regulation of immunity during health and disease

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

关键词: regulatory chemokines;    Tr‐;    1 cells;    cancer;    autoimmunity;    experimental autoimmune encephalomyelitis (EAE);    M2 macrophages;    D2 dendritic cells;   

DOI  :  10.1189/jlb.0909602

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Chemokinesareagroupofsmall,structurallyrelatedmoleculesthatregulatethetraffickingofvarioustypesofleukocytesthroughinteractionswithasubsetof7‐transmembraneG‐protein‐coupledreceptors.Askeychemoattractantsofinflammatoryleukocytes,chemokineshavebeenmarkedaspotentialtargetsforneutralizationinautoimmunediseases.Cancercellsalsoexpresschemokines,wheretheyfunctionassurvival/growthfactorsand/orangiogenicfactorsthatpromotetumordevelopmentandangiogenesis.Accordingly,thesefunctionsmakethemattractivetargetsfortherapyofthesediseases.Recently,wereportedthatoneofthesechemokinesCXCL12(SDF‐1α)functionsasananti‐inflammatorychemokineduringautoimmuneinflammatoryresponsesandexploredthemechanisticbasisofthisfunction.Asapleiotropicchemokine,CXCL12participatesintheregulationoftissuehomeostasis,immunesurveillance,autoimmunity,andcancer.ThischemokineisconstitutivelyexpressedintheBMandvarioustissues,whichenablesittoregulatethetraffickingandlocalizationofimmatureandmaturingleukocytes,includingBMstemcells,neutrophils,Tcells,andmonocyticcells.WehaveshownrecentlythatCXCL12increasesimmunologicaltoleranceinautoimmunediseasesbypolarizingTregsandbydoingso,restrainstheprogressionofthesediseases.ThisfindingsuggestsapossibleuseofstabilizedrCXCL12asapotentialdrugfortherapyofthesediseasesandtargetedneutralizationofCXCL12fortherapyofcancerdiseases.ThecurrentreviewexploresthedifferentbiologicalpropertiesofCXCL12anddiscussestheimplicationsofCXCL12‐basedtherapiesforautoimmunityandcancerdiseases...

【 授权许可】

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