| First Author | Almishri W | Year | 2016 |
| Journal | J Innate Immun | Volume | 8 |
| Issue | 6 | Pages | 617-629 |
| PubMed ID | 27560480 | Mgi Jnum | J:329086 |
| Mgi Id | MGI:6880692 | Doi | 10.1159/000448077 |
| Citation | Almishri W, et al. (2016) TNFalpha Augments Cytokine-Induced NK Cell IFNgamma Production through TNFR2. J Innate Immun 8(6):617-629 |
| abstractText | NK cells play a central role in innate immunity, acting directly through cell-mediated cytotoxicity and by secreting cytokines. TNFalpha activation of TNFR2 enhances NK cell cytotoxicity, but its effects on the other essential function of NK cells - cytokine production, for which IFNgamma is paramount - are poorly defined. We identify the expression of both TNFalpha receptors on human peripheral blood NK cells (TNFR2 > TNFR1) and show that TNFalpha significantly augments IFNgamma production from IL-2-/IL-12-treated NK cells in vitro, an effect mimicked by a TNFR2 agonistic antibody. TNFalpha also enhanced murine NK cell IFNgamma production via TNFR2 in vitro. In a mouse model characterized by the hepatic recruitment and activation of NK cells, TNFR2 also regulated NK cell IFNgamma production in vivo. Specifically, in this model, after activation of an innate immune response, hepatic numbers of TNFR2-expressing and IFNgamma-producing NK cells were both significantly increased; however, the frequency of IFNgamma-producing hepatic NK cells was significantly reduced in TNFR2-deficient mice. We delineate an important role for TNFalpha, acting through TNFR2, in augmenting cytokine-induced NK cell IFNgamma production in vivo and in vitro, an effect with significant potential implications for the regulation of innate and adaptive immune responses. |
