Human NK cells prime inflammatory DC precursors to induce Tc17 differentiation.
Blood Adv
; 4(16): 3990-4006, 2020 08 25.
Article
em En
| MEDLINE
| ID: mdl-32841340
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Células Matadoras Naturais
Limite:
Humans
Idioma:
En
Revista:
Blood Adv
Ano de publicação:
2020
Tipo de documento:
Article