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

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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Heink S,Yogev N,Garbers C,Herwerth M,Aly L,Gasperi C,Husterer V,Croxford AL,Möller-Hackbarth K,Bartsch HS,Sotlar K,Krebs S,Regen T,Blum H,Hemmer B,Misgeld T,Wunderlich TF,Hidalgo J,Oukka M,Rose-John S,Schmidt-Supp

doi

10.1038/ni.3632

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

74-85

issue

1

eissn

1529-2908

issn

1529-2916

pii

ni.3632

journal_volume

18

pub_type

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