Systemic administration of TLR3 agonist induces IL‐7 expression and IL‐7‐dependent CXCR3 ligand production in the lung

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

关键词: poly I:C;    IFN‐;    γ;    M1 macrophage;    chemokine;    effector T cells;    NK cells;   

DOI  :  10.1189/jlb.0712360

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inthisstudy,wetestedthehypothesisthatsystemicadministrationofTLR3agonistpolyI:CcanenhanceTcellinfiltrationoflungthroughup‐regulatingIL‐7expression.polyI:C,asyntheticanalogofviraldsRNAandaTLR3agonist,isstudiedextensivelyasvaccineadjuvantasaresultofitspleotropicimmune‐stimulatoryeffects.Here,weshowthatsystemicpolyI:CadministrationinducessubstantialIL‐7productioninthelunginatype1IFN‐andIFN‐γ‐dependentfashion.BlockadeoftheIL‐7RαsignalwithaneutralizingantibodyabrogatedpolyI:C‐inducedMCP‐1up‐regulation,macrophagerecruitment,andCXCR3ligandexpressioninthelung.Conversely,administrationofIL‐7enhancestheseevents,anditdoessobyenhancingTcellIFN‐γproduction.Wealsoshowthattheinitialup‐regulationofCXCR3ligandsandinfiltrationofTcellsinthelungaremediatedbypolyI:C‐inducedIFN‐γfromNKcells;however,thesustainedandoptimalCXCR3ligandexpressionandTcellinfiltrationrequirepolyI:C‐inducedIL‐7andTcell‐derivedIFN‐γ.InamodelofmultiorganinflammationelicitedbyadoptivetransferofimmunecellsintoRAG1−/−mice,weshowthatpolyI:CenhancesIL‐7productioninthelungandpromotesexpressionofCXCR3ligandsandrecruitmentofIFN‐γ+TcellsinanIL‐7‐dependentfashion.Collectively,theseresultsstronglysupportourhypothesisanddelineateanewmechanismbywhichpolyI:CbooststheTcellimmuneresponseinthelungbyinducinglocalIL‐7production,whichinturn,enhancesTcell‐derivedIFN‐γtopromotemacrophagerecruitment,CXCR3ligandexpression,andTcellinfiltration...

【 授权许可】

CC BY