tetano
Editor, Senior Moderator
Sci Rep. 2019 Mar 21;9(1):4984. doi: 10.1038/s41598-019-41478-6.
[h=1]IL-27 promotes NK cell effector functions via Maf-Nrf2 pathway during influenza infection.[/h] Kumar P[SUP]1[/SUP], Rajasekaran K[SUP]1[/SUP], Nanbakhsh A[SUP]1[/SUP], Gorski J[SUP]2[/SUP], Thakar MS[SUP]1,[/SUP][SUP]3[/SUP], Malarkannan S[SUP]4,[/SUP][SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-γ). 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[SUP]-/-[/SUP]) or IL-27 (Ebi3[SUP]-/-[/SUP]) resulted in impaired NK cell effector functions including the generation of anti-viral IFN-γ responses. We identify CD27[SUP]+[/SUP]CD11b[SUP]+[/SUP] NK cells as the primary subset that expresses IL-27R, which predominantly produces IFN-γ 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.
PMID: 30899058 DOI: 10.1038/s41598-019-41478-6
[h=1]IL-27 promotes NK cell effector functions via Maf-Nrf2 pathway during influenza infection.[/h] Kumar P[SUP]1[/SUP], Rajasekaran K[SUP]1[/SUP], Nanbakhsh A[SUP]1[/SUP], Gorski J[SUP]2[/SUP], Thakar MS[SUP]1,[/SUP][SUP]3[/SUP], Malarkannan S[SUP]4,[/SUP][SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-γ). 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[SUP]-/-[/SUP]) or IL-27 (Ebi3[SUP]-/-[/SUP]) resulted in impaired NK cell effector functions including the generation of anti-viral IFN-γ responses. We identify CD27[SUP]+[/SUP]CD11b[SUP]+[/SUP] NK cells as the primary subset that expresses IL-27R, which predominantly produces IFN-γ 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.
PMID: 30899058 DOI: 10.1038/s41598-019-41478-6