| First Author | Wang X | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 35 | Pages | 17409-17418 |
| PubMed ID | 31405974 | Mgi Jnum | J:284308 |
| Mgi Id | MGI:6359079 | Doi | 10.1073/pnas.1904125116 |
| Citation | Wang X, et al. (2019) 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 |
| abstractText | 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. |
