2. Academic Validation
  3. Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells

Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells

  • Nat Immunol. 2017 Jan;18(1):74-85. doi: 10.1038/ni.3632.
Sylvia Heink 1,  Nir Yogev 2,  Christoph Garbers 3,  Marina Herwerth 1 4,  Lilian Aly 1,  Christiane Gasperi 1,  Veronika Husterer 1,  Andrew L Croxford 2,  Katja Möller-Hackbarth 3,  Harald S Bartsch 5,  Karl Sotlar 5,  Stefan Krebs 6,  Tommy Regen 2,  Helmut Blum 6,  Bernhard Hemmer 1 7,  Thomas Misgeld 4 7,  Thomas F Wunderlich 8,  Juan Hidalgo 9,  Mohamed Oukka 10 11,  Stefan Rose-John 3,  Marc Schmidt-Supprian 12,  Ari Waisman 2,  Thomas Korn 1 7
Affiliations

Affiliations

  • 1 Klinikum rechts der Isar, Department of Neurology, Technical University of Munich, Munich, Germany.
  • 2 Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
  • 3 Institute of Biochemistry, Kiel University, Kiel, Germany.
  • 4 Institute of Neuronal Cell Biology, Technical University of Munich, Munich, Germany.
  • 5 Institute of Pathology, Medical School, Ludwig-Maximilians-University, Munich, Germany.
  • 6 Gene Centre, Lafuga, Ludwig-Maximilians-University, Munich, Germany.
  • 7 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
  • 8 Max Planck Institute for Metabolism Research, Cologne, Germany.
  • 9 Department of Cellular Biology, Physiology, and Immunology, Autonomous University of Barcelona, Barcelona, Spain.
  • 10 Department of Immunology, University of Washington, Seattle, Washington, USA.
  • 11 Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA.
  • 12 Department of Hematology and Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
PMID: 27893700 DOI: 10.1038/ni.3632
Abstract

The cellular sources of interleukin 6 (IL-6) that are relevant for differentiation of the TH17 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 TH17 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 (IFN-γ) expression in T cells and to generate pathogenic TH17 cells in vivo. Our findings should guide therapeutic approaches for the treatment of TH17-cell-mediated autoimmune diseases.

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