Jak/STAT and PI3K signaling pathways have both common and distinct roles in IL‐7‐mediated activities in human CD8+ T cells

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

关键词: cytokines;    lymphocytes;    proliferation;   

DOI  :  10.1189/jlb.0313122

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

IL‐7playsanimportantroleinTcellsurvival,function,andmemorycelldevelopment,yettheroleofcytokinesignalingpathwaysintheseprocesseshasnotbeenfullyelucidated.Moreover,theunderlyingmechanismsfortheobservedimpairmentofIL‐7activityindiseases,suchasHIVinfection,breastcancer,andautoimmunity,arenotwellunderstood.ItwasthereforehypothesizedthatIL‐7‐inducedsignalingmoleculescouldbelinkedwithdistinctIL‐7‐associatedactivities.Toaddressthis,theactivationandfunctionalassociationsofIL‐7‐inducedsignalingpathways,specificallyantigen‐independentactivitiesthatarerelevanttoTcellhomeostasis,wereexamined.LowconcentrationsofIL‐7(100pg/ml)arecapableofactivatingtheJak‐STATandPI3Ksignalingpathways,whereashigherconcentrations(500–1000pg/ml)wererequiredtoinduceBcl‐2productionandglucoseuptake.EvenhigherconcentrationsofIL‐7(10,000pg/ml)wereneededtoinducecellproliferationandintracellularaccumulationofperforin.InhibitionofJakactivationreducedIL‐7‐inducedBcl‐2andperforinproduction,whereasinhibitionofJak/STATorPI3Kpathwaysreducedglucoseuptakeandproliferation.ThisstudysuggestsacomplexcontrolofIL‐7‐associatedactivitiesintheabsenceofantigenstimulation.ThesedatamayprovideinsightsintomechanismsofimpairedIL‐7signalingandfunctionindiseaseandcouldberelevantforthestudyofIL‐7‐basedimmunotherapeutics.Specifically,thisstudyhaslinkedSTAT5andPI3KactivationtosharedanddistinctIL‐7‐associatedactivitiesinhumanCD8+Tcells...

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