Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T H 17 cells

Sylvia Heink, Nir Yogev, Christoph Garbers, Marina Herwerth, Lilian Aly, Christiane Gasperi, Veronika Husterer, Andrew L. Croxford, Katja Möller-Hackbarth, Harald S. Bartsch, Karl Sotlar, Stefan Krebs, Tommy Regen, Helmut Blum, Bernhard Hemmer, Thomas Misgeld, Thomas F. Wunderlich, Juan Hidalgo, Mohamed Oukka, Stefan Rose-JohnMarc Schmidt-Supprian, Ari Waisman, Thomas Korn

Research output: Contribution to journalArticleResearchpeer-review

153 Citations (Scopus)

Abstract

The cellular sources of interleukin 6 (IL-6) that are relevant for differentiation of the T H 17 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 H 17 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 3 (IFN-γ 3) expression in T cells and to generate pathogenic T H 17 cells in vivo. Our findings should guide therapeutic approaches for the treatment of T H 17-cell-mediated autoimmune diseases.
Original languageEnglish
Pages (from-to)74-85
JournalNature Immunology
Volume18
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017

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