| First Author | Heink S | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 1 | Pages | 74-85 |
| PubMed ID | 27893700 | Mgi Jnum | J:260609 |
| Mgi Id | MGI:6142555 | Doi | 10.1038/ni.3632 |
| Citation | Heink S, et al. (2017) Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells. Nat Immunol 18(1):74-85 |
| abstractText | 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 Sirpalpha were essential for the generation of pathogenic TH17 cells. Using their IL-6 receptor alpha-chain (IL-6Ralpha), Sirpalpha(+) 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-6Ralpha (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. |
