Deconvoluting global cytokine signaling networks in natural killer cells.
Nat Immunol
; 22(5): 627-638, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33859404
ABSTRACT
Cytokine signaling via signal transducer and activator of transcription (STAT) proteins is crucial for optimal antiviral responses of natural killer (NK) cells. However, the pleiotropic effects of both cytokine and STAT signaling preclude the ability to precisely attribute molecular changes to specific cytokine-STAT modules. Here, we employed a multi-omics approach to deconstruct and rebuild the complex interaction of multiple cytokine signaling pathways in NK cells. Proinflammatory cytokines and homeostatic cytokines formed a cooperative axis to commonly regulate global gene expression and to further repress expression induced by type I interferon signaling. These cytokines mediated distinct modes of epigenetic regulation via STAT proteins, and collective signaling best recapitulated global antiviral responses. The most dynamically responsive genes were conserved across humans and mice, which included a cytokine-STAT-induced cross-regulatory program. Thus, an intricate crosstalk exists between cytokine signaling pathways, which governs NK cell responses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Interleucinas
/
Infecções por Herpesviridae
/
Epigênese Genética
/
Fatores de Transcrição STAT
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article