Soluble Immune Complexes Shift the TLR-Induced Cytokine Production of Distinct Polarized Human Macrophage Subsets towards IL-10 英文参考文献.docVIP

Soluble Immune Complexes Shift the TLR-Induced Cytokine Production of Distinct Polarized Human Macrophage Subsets towards IL-10 英文参考文献.doc

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Soluble Immune Complexes Shift the TLR-Induced Cytokine Production of Distinct Polarized Human Macrophage Subsets towards IL-10 英文参考文献

SolubleImmuneComplexesShifttheTLR-Induced CytokineProductionofDistinctPolarizedHuman MacrophageSubsetstowardsIL-10 CarmenA.Ambarus1*,KimC.M.Santegoets2,LennyvanBon2,MarkH.Wenink2,PaulP.Tak1, TimothyR.D.J.Radstake2,DominiqueL.P.Baeten1 1Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands, 2Department of Rheumatology,RadboudUniversityNijmegenMedicalCenter,Nijmegen,TheNetherlands Abstract Background: Costimulation of murine macrophages with immune complexes (ICs) and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production.Thisstudyaimed toclarifytheeffectofICsonthepro-versusanti-inflammatory profileofhumanpolarized macrophages. MaterialsandMethods:MonocytesisolatedfromperipheralbloodofhealthydonorswerepolarizedforfourdayswithIFN- c,IL-4,IL-10,GM-CSF,M-CSF,orLPS,inthepresenceorabsenceofheataggregatedgamma-globulins(HAGGs).Phenotypic polarization markers were measured by flow cytometry. Polarized macrophages were stimulated with HAGGs or immobilizedIgGaloneorincombinationwithTLRligands.TNF,IL-6,IL-10,IL-12,andIL-23weremeasuredbyLuminexand/ orRT-qPCR. Results: HAGGs did not modulate the phenotypic polarization and the cytokine production of macrophages. However, HAGGssignificantlyalteredtheTLR-inducedcytokineproductionofallpolarizedmacrophagesubsets,withtheexceptionof MWIL-4.Inparticular,HAGGs consistently enhancedtheTLR-inducedIL-10production inboth classicallyandalternatively polarizedmacrophages(M1andM2).TheeffectofHAGGsonTNFandIL-6productionwaslesspronouncedanddepended onthepolarizationstatus,whileIL-23p19andIL-12p35expressionwasnotaffected.IncontrastwithHAGGs,immobilized IgGinducedastrongupregulationofnotonlyIL-10,butalsoTNFandIL-6. Conclusion:HAGGsalonedonotalterthephenotypeandcytokineproductionofinvitropolarizedhumanmacrophages.In combination with TLR-ligands, however, HAGGs

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