Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells
Nature immunology. Bd. 18. H. 1. New York, NY: Nature America Inc. 2017 S. 74 - 85
Erscheinungsjahr: 2017
ISBN/ISSN: 1529-2916 ; 1529-2908
Publikationstyp: Zeitschriftenaufsatz
Sprache: Englisch
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Inhaltszusammenfassung
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 Sirp[alpha] were essential for the generation of pathogenic TH17 cells. Using their IL-6 receptor [alpha]-chain (IL-6R[alpha]), Sirp[alpha]+ DCs trans-presented IL-6 to T cells during the proc...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 Sirp[alpha] were essential for the generation of pathogenic TH17 cells. Using their IL-6 receptor [alpha]-chain (IL-6R[alpha]), Sirp[alpha]+ 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-6R[alpha] (called 'IL-6 cluster signaling' here) was needed to prevent premature induction of interferon-[gamma] (IFN-[gamma]) 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. ER» weiterlesen» einklappen
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Medizin
