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Nat Immunol. 2017 Jan;18(1):74-85. doi: 10.1038/ni.3632. Epub 2016 Nov 28.

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

Author information

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.

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.

PMID:
27893700
PMCID:
PMC5164931
DOI:
10.1038/ni.3632
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no competing financial interest.

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