Endogenously produced TNF‐α contributes to the expression of CXCL10/IP‐10 in IFN‐λ3‐activated plasmacytoid dendritic cells

[摘要] TheinterplaybetweenIFN‐λsanddendriticcellsisbecomingincreasinglyrelevant,particularlyinlightoftheirkeyroleininducingtheantiviralstate,includinginhepatitisCvirusinfection.Inthiswork,wehaveanalyzedextensivelyhowhumanplasmacytoiddendriticcellsrespondtoIFN‐λ3.WereportthatplasmacytoiddendriticcellsincubatedwithIFN‐λ3prolongtheirsurvival;altertheirexpressionpatternofsurfaceHLA‐DRα,CD123,CD86,andCD303;andtimedependentlyproduceIFN‐α,CXCL10/IFN‐γ‐inducedprotein10,andevenmodestquantitiesofTNF‐α.Nevertheless,endogenouslyproducedTNF‐α,butnotIFN‐α,wasfoundtobeessentialfordrivingtheexpressionofCXCL10/IFN‐γ‐inducedprotein10inIFN‐λ3‐treatedplasmacytoiddendriticcells,asrevealedbyneutralizingexperimentsbyuseofadalimumab,etanercept,andinfliximab.WealsoobservedthatbasedonthekineticsandlevelsofIFN‐αandCXCL10/IFN‐γ‐inducedprotein10producedbytheirIFN‐λ3‐treatedplasmacytoiddendriticcells,healthydonorscouldbecategorizedinto2and3groups,respectively.Inparticular,weidentifiedagroupofdonorswhoseplasmacytoiddendriticcellsproducedmodestquantitiesofCXCL10/IFN‐γ‐inducedprotein10;anotheronewhoseplasmacytoiddendriticcellsproducedelevatedCXCL10/IFN‐γ‐inducedprotein10levels,alreadyafter18h,decliningthereafter;anda3rdgroupcharacterizedbyplasmacytoiddendriticcellsreleasingveryhighCXCL10/IFN‐γ‐inducedprotein10levelsafter42honly.Finally,wereportthatinplasmacytoiddendriticcells,equivalentconcentrationsofIFN‐λ3andIFN‐λ1promotesurvival,antigenmodulation,andcytokineproductioninacomparablemannerandwithoutactingadditively/synergistically.Altogether,datanotonlyextendtheknowledgeonthebiologiceffectsthatIFN‐λsexertonplasmacytoiddendriticcellsbutalsoaddnovellighttothenetworkingbetweenIFN‐λsandplasmacytoiddendriticcellsinfightingviraldiseases...

[学科分类] 生理学

[关键词] pDCs;innate immunity;interferons;antiviral response