IL-27 promotes NK cell effector functions via Maf-Nrf2 pathway during influenza infection. Sci Rep 2019 Mar 21;9(1):4984
Date
03/23/2019Pubmed ID
30899058Pubmed Central ID
PMC6428861DOI
10.1038/s41598-019-41478-6Scopus ID
2-s2.0-85063320720 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
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-/-) or IL-27 (Ebi3-/-) resulted in impaired NK cell effector functions including the generation of anti-viral IFN-γ responses. We identify CD27+CD11b+ 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.
Author List
Kumar P, Rajasekaran K, Nanbakhsh A, Gorski J, Thakar MS, Malarkannan SAuthor
Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntigens, CD
Bronchoalveolar Lavage
Cell Death
Female
Interferon-gamma
Interleukin-12
Interleukin-27
Interleukins
Killer Cells, Natural
Maf Transcription Factors
Male
Mice, Inbred C57BL
Minor Histocompatibility Antigens
NF-E2-Related Factor 2
NK Cell Lectin-Like Receptor Subfamily A
NK Cell Lectin-Like Receptor Subfamily K
Orthomyxoviridae Infections
Receptors, Cytokine
Receptors, Interleukin
Signal Transduction
