biostudies-literatureHeink SEuropean Research CouncilNIAID NIH HHS74-85https://www.ebi.ac.uk/biostudies/studies/S-EPMC5164931biostudies-literatureUnknown18(1)The cellular sources of interleukin 6 (IL-6) that are relevant for differentiation of the T_H17 subset of helper T cells remain unclear. Here we used a novel strategy for the conditional deletion of distinct IL-6-producing cell types to show that dendritic cells (DCs) positive for the signaling regulator Sirpα were essential for the generation of pathogenic T_H17 cells. Using their IL-6 receptor α-chain (IL-6Rα), Sirpα⁺ DCs trans-presented IL-6 to T cells during the process of cognate interaction. While ambient IL-6 was sufficient to suppress the induction of expression of the transcription factor Foxp3 in T cells, trans-presentation of IL-6 by DC-bound IL-6Rα (called 'IL-6 cluster signaling' here) was needed to prevent premature induction of interferon-γ (IFNature immunologyTrans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T<sub>H</sub>17 cells.PMC5164931647215R21 AI124735Oukka MBartsch HSRegen TBlum HMisgeld TMoller-Hackbarth KHusterer VRose-John SHeink SSchmidt-Supprian MWaisman AWunderlich TFGarbers CHidalgo JGasperi CHemmer BSotlar KHerwerth MKorn TCroxford ALKrebs SAly LYogev NfalseTrans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T<sub>H</sub>17 cells.The cellular sources of interleukin 6 (IL-6) that are relevant for differentiation of the T_H17 subset of helper T cells remain unclear. Here we used a novel strategy for the conditional deletion of distinct IL-6-producing cell types to show that dendritic cells (DCs) positive for the signaling regulator Sirpα were essential for the generation of pathogenic T_H17 cells. Using their IL-6 receptor α-chain (IL-6Rα), Sirpα⁺ DCs trans-presented IL-6 to T cells during the process of cognate interaction. While ambient IL-6 was sufficient to suppress the induction of expression of the transcription factor Foxp3 in T cells, trans-presentation of IL-6 by DC-bound IL-6Rα (called 'IL-6 cluster signaling' here) was needed to prevent premature induction of interferon-γ (IF2017-01-01T00:00:00Z2017 Jan2026-04-28T23:52:50.541Z2019-03-27T02:31:47ZS-EPMC51649312789370010.1038/ni.3632