6533b870fe1ef96bd12cf2d9
RESEARCH PRODUCT
Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells
Andrew L. CroxfordBernhard HemmerLilian AlyStefan Rose JohnNir YogevTommy RegenMarina HerwerthJuan HidalgoChristoph GarbersStefan KrebsThomas MisgeldVeronika HustererHelmut BlumThomas WunderlichHarald BartschAri WaismanSylvia HeinkThomas KornKarl SotlarMohamed OukkaMohamed OukkaMarc Schmidt-supprianKatja Möller-hackbarthChristiane Gasperisubject
0301 basic medicineCell typebiologyCellular differentiationImmunologyLymphocyte differentiationFOXP3Priming (immunology)medicine.disease_cause3. Good healthCell biologyAutoimmunity03 medical and health sciences030104 developmental biology0302 clinical medicineImmunologybiology.proteinmedicineImmunology and AllergyInterleukin 6Transcription factor030215 immunologydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-11-28 | Nature Immunology |