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PolyI:C plus IL-2 or IL-12 induce IFN-γ production by human NK cells via autocrine IFN-β

Abstract : NK lymphocytes and type I IFN (IFN-a/b) are major actors of the innate anti-viral response that also influence adaptive immune responses. We evaluated type I IFN production by human NK cells in response to polyI:C, a potent type I IFN-inducing TLR3 agonist. PolyI:C plus IL-2/IL-12 induced IFN-b (but not IFN-a) mRNA expression and protein production by highly pure human NK cells and by the human NK cell line NK92. Neutralizing anti-IFNAR1 or anti-IFN-b Ab prevented the production of IFN-gamma induced by polyI:C plus IL-2/IL-12. Similarly, IFN-gamma production induced by polyI:C plus IL-12 was reduced in NK cells isolated from IFNAR1 -/- compared with WT mice. The ability of polyI:C plus IL-12 to induce IFN-gamma production was related to an increase of TLR3, Mda5 and IFNAR expression and by an increase of STAT1 and STAT4 phosphorylation. Collectively, these data demonstrate that NK cells, in response to polyI:C plus IL-2/IL-12, produce IFN-b that induce, in an autocrine manner, the production of IFN-gamma and thereby highlight that NK cells may control the outcome of protective or injurious immune responses through type I IFN secretion.
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https://www.hal.inserm.fr/inserm-03377780
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Submitted on : Thursday, October 14, 2021 - 12:08:20 PM
Last modification on : Sunday, June 26, 2022 - 12:17:48 PM
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Dorothée Duluc, Fang Tan, Mari Scotet, Simon J. Blanchard, Isabelle Frémaux, et al.. PolyI:C plus IL-2 or IL-12 induce IFN-γ production by human NK cells via autocrine IFN-β. European Journal of Immunology, Wiley-VCH Verlag, 2009, 39 (10), pp.2877 - 2884. ⟨10.1002/eji.200838610⟩. ⟨inserm-03377780⟩

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