Human β‐defensin 3 induces STAT1 phosphorylation, tyrosine phosphatase activity, and cytokine synthesis in T cells

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

关键词: T lymphocyte;    antimicrobial peptides;    signal transduction;    IL‐;    2;    IL‐;    10;    IFN‐;    γ;   

DOI  :  10.1189/jlb.0612300

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TheAMPhBD‐3stimulatesnumerousimmuneeffectorfunctionsinmyeloidcellsandkeratinocytes,predominantlythroughtheMAPKsignalingcascade.Incontrast,hBD‐3wasreportedtoneutralizetheactivationofTcellsbyantagonizingMAPKsignalinginitiatedbySDF‐1αthroughCXCR4.Withtheuseofcomplementaryproteomicandimmunochemicalapproaches,weinvestigatedpossiblestimulatoryeffectsofhBD‐3onTcellsanddemonstratethathBD‐3inducesSTAT1tyrosinephosphorylationwithin5minyetisunabletoinduceMAPKactivation.InclusionofaPTPaseinhibitorincreasedhBD‐3‐inducedphosphorylationdramatically,suggestingthathBD‐3alsostimulatesPTPaseactivityconcurrently.TheincreaseinPTPaseactivitywasconfirmedbydemonstratingthathBD‐3suppressesIFN‐γ‐inducedSTAT1tyrosinephosphorylationbutnotSTAT1serineandERK1/2threoninephosphorylationandstimulatesthetranslocationofSHP‐2intothenucleuswithin15min.ThesignalingpathwaysinitiatedbyhBD‐3mayleadtotheobservedenhancementofdistinctTcelleffectorfunctionsduringTCRactivation,suchastheincreaseinIL‐2andIL‐10,butnotIFN‐γsecretion.Thus,hBD‐3initiatesdistinctlineage‐specificsignalingcascadesinvariouscellsinvolvedinhostdefenseandinducesaconcurrenttyrosinekinaseandtyrosinephosphatasesignalingcascadethatmayactivatesimultaneouslythetargetedTcellsandinhibittheirresponsetootherimmunemediators.Furthermore,theseresultssuggestthatthisevolutionarilyconservedpeptide,whichexhibitsabroadspectrumofantimicrobialandimmunomodulatoryactivities,servestointegrateinnateandadaptiveimmunity...

【 授权许可】

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