1. Human NK cells prime inflammatory DC precursors to induce Tc17 differentiation
- Author
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Maria Alejandra Clavijo-Salomon, Giorgio Trinchieri, Amiran Dzutsev, José Alexandre Marzagão Barbuto, Jordan S. Orange, Helioswilton Sales-Campos, Rosalba Salcedo, Lucia Silla, Karen S.C. Borbely, Emily M. Mace, Rodrigo X. Das Neves, and Soumen Roy
- Subjects
Innate immune system ,Immunobiology and Immunotherapy ,CD14 ,GATA2 ,Priming (immunology) ,Cell Differentiation ,Hematology ,Dendritic Cells ,CD16 ,Biology ,Cell biology ,Killer Cells, Natural ,Interferon-gamma ,Immune system ,Immunity ,DIFERENCIAÇÃO CELULAR ,Humans ,CD8 ,Cells, Cultured - Abstract
Adaptive immune responses are acknowledged to evolve from innate immunity. However, limited information exists regarding whether encounters between innate cells direct the generation of specialized T-cell subsets. We aim to understand how natural killer (NK) cells modulate cell-mediated immunity in humans. We found that human CD14+CD16− monocytes that differentiate into inflammatory dendritic cells (DCs) are shaped at the early stages of differentiation by cell-to-cell interactions with NK cells. Although a fraction of monocytes is eliminated by NK-cell–mediated cytotoxicity, the polarization of interferon-γ (IFN-γ) at the NKp30-stabilized synapses triggers a stable IFN-γ signature in surviving monocytes that persists after their differentiation into DCs. Notably, NK-cell–instructed DCs drive the priming of type 17 CD8+ T cells (Tc17) with the capacity to produce IFN-γ and interleukin-17A. Compared with healthy donors, this cellular network is impaired in patients with classical NK-cell deficiency driven by mutations in the GATA2 gene. Our findings reveal a previously unrecognized connection by which Tc17-mediated immunity might be regulated by NK-cell–mediated tuning of antigen-presenting cells.
- Published
- 2020