Clusterin synergizes with IL‐2 for the expansion and IFN‐γ production of natural killer cells

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

关键词: cell proliferation;    NK activation markers;    natural cytotoxicity;    immune function;   

DOI  :  10.1189/jlb.0310157

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CLUisasecreted,multifunctionalproteinimplicatedinseveralimmunologicandpathologicconditions.AsthelevelofserumCLUwasshowntobeelevatedduringinflammatoryresponses,wequestionedifCLUmightinteractwithcirculatinglymphocytesleadingtofunctionalconsequences.Toassessthispossibilitydirectly,mousesplenocytesandpurifiedNKcellswereculturedwithvaryingdoseofCLU,anditseffectoncellproliferationwasexamined.OurdatashowedthatCLUup‐regulatedDNAsynthesisandexpansionofNKcellssignificantlyinresponsetoasuboptimal,butnotmaximal,doseofIL‐2,andCLUalonedidnotexhibitsucheffects.ThisCLU‐mediatedsynergyrequiredthecopresenceofCLUattheonsetofIL‐2stimulationandneededacontinuouspresenceduringtherestoftheculture.Importantly,NKcellsstimulatedwithCLUshowedincreasedformationofcellclustersandaCD69activationreceptor,representingahighercellularactivationstatuscomparedwiththosefromthecontrolgroup.Furthermore,theseNKcellsdisplayedelevatedIFN‐γproductionuponRMA/Stumortargetexposures,implyingthatCLUregulatesnotonlyNKcellexpansionbutalsoeffectorfunctionofNKcells.Collectively,ourdatapresentapreviouslyunrecognizedfunctionofCLUasanovelregulatorofNKcellsviaprovidingcostimulationrequiredforcellproliferationandIFN‐γsecretion.Therefore,theroleofCLUonNKcellsshouldbetakenintoconsiderationforthepreviouslyobserved,diversefunctionsofCLUinchronicinflammatoryandautoimmuneconditions...

【 授权许可】

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