Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells.
Nat Immunol
; 18(1): 74-85, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-27893700
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Sistema Nervoso Central
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Interleucina-6
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Encefalomielite Autoimune Experimental
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Subunidade alfa de Receptor de Interleucina-6
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Células Th17
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article