Stromal fibroblasts support dendritic cells to maintain IL‐23/Th17 responses after exposure to ionizing radiation

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

关键词: cytokine;    immunity;    cancer;   

DOI  :  10.1189/jlb.3A1015-474R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Dendriticcellfunctionismodulatedbystromalcells,includingfibroblasts.Althoughpoorlyunderstood,thesignalsdeliveredthroughthiscrosstalksubstantiallyalterdendriticcellbiology.ThisiswellillustratedwithreleaseofTNF‐α/IL‐1βfromactivateddendriticcells,promotingPGE2secretionfromstromalfibroblasts.Thisinstructsdendriticcellstoup‐regulateIL‐23,akeyTh17‐polarizingcytokine.WepreviouslyshowedthationizingradiationinhibitedIL‐23productionbyhumandendriticcellsinvitro.Inthepresentstudy,weinvestigatedthehypothesisthatdendriticcell‐fibroblastcrosstalkovercomesthesuppressiveeffectofionizingradiationtosupportappropriatelypolarizedTh17responses.Radiation(1–6Gy)markedlysuppressedIL‐23secretionbyactivateddendriticcells(P<0.0001)withoutadverselyimpactingtheirviabilityandconsequently,inhibitedthegenerationofTh17responses.Cytokinesuppressionbyionizingradiationwasselective,astherewasnoeffectonIL‐1β,‐6,‐10,and‐27orTNF‐αandonlyamodest(11%)decreaseinIL‐12p70secretion.CoculturewithfibroblastsaugmentedIL‐23secretionbyirradiateddendriticcellsandincreasedTh17responses.Importantly,incontrasttodendriticcells,irradiatedfibroblastsmaintainedtheircapacitytorespondtoTNF‐α/IL‐1βandproducePGE2,thusprovidingthekeyintermediarysignalsforsuccessfuldendriticcell‐fibroblastscrosstalk.Insummary,stromalfibroblastssupportTh17‐polarizingcytokineproductionbydendriticcellsthatwouldotherwisebesuppressedinanirradiatedmicroenvironment.Thishaspotentialramificationsforunderstandingtheimmuneresponsetolocalradiotherapy.Thesefindingsunderscoretheneedtoaccountfortheimpactofmicroenvironmentalfactors,includingstromalcells,inunderstandingthecontrolofimmunity...

【 授权许可】

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