Human NK cells prime inflammatory DC precursors to induce Tc17 differentiation
Open Access
- 25 August 2020
- journal article
- research article
- Published by American Society of Hematology in Blood Advances
- Vol. 4 (16), 3990-4006
- https://doi.org/10.1182/bloodadvances.2020002084
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-gamma (IFN-gamma) at the NKp30-stabilized synapses triggers a stable IFN-gamma 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-gamma 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.Keywords
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