IL-17 constrains natural killer cell activity by restraining IL-15-driven cell maturation via SOCS3.
Proc Natl Acad Sci U S A
; 116(35): 17409-17418, 2019 08 27.
Article
em En
| MEDLINE
| ID: mdl-31405974
ABSTRACT
Increasing evidence demonstrates that IL-17A promotes tumorigenesis, metastasis, and viral infection. Natural killer (NK) cells are critical for defending against tumors and infections. However, the roles and mechanisms of IL-17A in regulating NK cell activity remain elusive. Herein, our study demonstrated that IL-17A constrained NK cell antitumor and antiviral activity by restraining NK cell maturation. It was observed that the development and metastasis of tumors were suppressed in IL-17A-deficient mice in the NK cell-dependent manner. In addition, the antiviral activity of NK cells was also improved in IL-17A-deficient mice. Mechanistically, ablation of IL-17A signaling promoted generation of terminally mature CD27-CD11b+ NK cells, whereas constitutive IL-17A signaling reduced terminally mature NK cells. Parabiosis or mixed bone marrow chimeras from Il17a-/- and wild-type (WT) mice could inhibit excessive generation of terminally mature NK cells induced by IL-17A deficiency. Furthermore, IL-17A desensitized NK cell responses to IL-15 and suppressed IL-15-induced phosphorylation of signal transducer and activator of transcription 5 (STAT5) via up-regulation of SOCS3, leading to down-regulation of Blimp-1. Therefore, IL-17A acts as the checkpoint during NK cell terminal maturation, which highlights potential interventions to defend against tumors and viral infections.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Interleucina-15
/
Interleucina-17
/
Proteína 3 Supressora da Sinalização de Citocinas
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China