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TNFα Augments Cytokine-Induced NK Cell IFNγ Production through TNFR2.
- Source :
-
Journal of innate immunity [J Innate Immun] 2016; Vol. 8 (6), pp. 617-629. Date of Electronic Publication: 2016 Aug 25. - Publication Year :
- 2016
-
Abstract
- NK cells play a central role in innate immunity, acting directly through cell-mediated cytotoxicity and by secreting cytokines. TNFα activation of TNFR2 enhances NK cell cytotoxicity, but its effects on the other essential function of NK cells - cytokine production, for which IFNγ is paramount - are poorly defined. We identify the expression of both TNFα receptors on human peripheral blood NK cells (TNFR2 > TNFR1) and show that TNFα significantly augments IFNγ production from IL-2-/IL-12-treated NK cells in vitro, an effect mimicked by a TNFR2 agonistic antibody. TNFα also enhanced murine NK cell IFNγ production via TNFR2 in vitro. In a mouse model characterized by the hepatic recruitment and activation of NK cells, TNFR2 also regulated NK cell IFNγ production in vivo. Specifically, in this model, after activation of an innate immune response, hepatic numbers of TNFR2-expressing and IFNγ-producing NK cells were both significantly increased; however, the frequency of IFNγ-producing hepatic NK cells was significantly reduced in TNFR2-deficient mice. We delineate an important role for TNFα, acting through TNFR2, in augmenting cytokine-induced NK cell IFNγ production in vivo and in vitro, an effect with significant potential implications for the regulation of innate and adaptive immune responses.<br /> (© 2016 S. Karger AG, Basel.)
- Subjects :
- Animals
Antibodies, Blocking pharmacology
Cells, Cultured
Cytotoxicity, Immunologic
Humans
Immunity, Innate
Interferon-gamma genetics
Interferon-gamma metabolism
Interleukin-12 immunology
Interleukin-2 immunology
Lymphocyte Activation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Tumor Necrosis Factor, Type II genetics
Signal Transduction
Tumor Necrosis Factor-alpha immunology
Killer Cells, Natural immunology
Receptors, Tumor Necrosis Factor, Type II metabolism
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1662-8128
- Volume :
- 8
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of innate immunity
- Publication Type :
- Academic Journal
- Accession number :
- 27560480
- Full Text :
- https://doi.org/10.1159/000448077