Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Clusterin synergizes with IL‐2 for the expansion and IFN‐γ production of natural killer cells | |
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...
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