| First Author | Kumar P | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 4984 |
| PubMed ID | 30899058 | Mgi Jnum | J:276671 |
| Mgi Id | MGI:6307352 | Doi | 10.1038/s41598-019-41478-6 |
| Citation | Kumar P, et al. (2019) IL-27 promotes NK cell effector functions via Maf-Nrf2 pathway during influenza infection. Sci Rep 9(1):4984 |
| abstractText | Influenza virus targets epithelial cells in the upper respiratory tract. Natural Killer (NK) cell-mediated early innate defense responses to influenza infection include the killing of infected epithelial cells and generation of anti-viral cytokines including interferon gamma (IFN-gamma). To date, it is unclear how the underlying cytokine milieu during infection regulates NK cell effector functions. Our data show during influenza infection myeloid cell-derived IL-27 regulates the early-phase effector functions of NK cells in the bronchioalveolar and lung tissue. Lack of IL-27R (Il27ra(-/-)) or IL-27 (Ebi3(-/-)) resulted in impaired NK cell effector functions including the generation of anti-viral IFN-gamma responses. We identify CD27(+)CD11b(+) NK cells as the primary subset that expresses IL-27R, which predominantly produces IFN-gamma within the upper respiratory tract of the infected mice. IL-27 alone was incapable of altering the effector functions of NK cells. However, IL-27 sensitizes NK cells to augment both in vitro and in vivo responses mediated via the NKG2D receptor. This 'priming' function of IL-27 is mediated partly via transcriptional pathways regulated by Mafs and Nrf2 transcriptionally regulating TFAM and CPT1. Our data for the first time establishes a novel role for IL-27 in regulating early-phase effector functions of NK cells during influenza infection. |
