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 Sirp alpha were essential for the generation of pathogenic T(H)17 cells. Using their IL-6 receptor a-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 T(H)17 cells in vivo. Our findings should guide therapeutic approaches for the treatment of T(H)17-cell-mediated autoimmune diseases.
Item Type: | Journal article |
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Faculties: | Medicine Chemistry and Pharmacy > Department of Biochemistry |
Subjects: | 600 Technology > 610 Medicine and health 500 Science > 540 Chemistry |
ISSN: | 1529-2908 |
Language: | English |
Item ID: | 49973 |
Date Deposited: | 14. Jun 2018, 09:42 |
Last Modified: | 04. Nov 2020, 13:27 |