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- Title
PolyI:C plus IL-2 or IL-12 induce IFN-γ production by human NK cells via autocrine IFN-β.
- Authors
Duluc, Dorothée; Tan, Fang; Scotet, Mari; Blanchard, Simon; Frémaux, Isabelle; Garo, Erwan; Horvat, Branka; Eid, Pierre; Delneste, Yves; Jeannin, Pascale
- Abstract
NK lymphocytes and type I IFN (IFN-α/β) 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-β (but not IFN-α) 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-β Ab prevented the production of IFN-γ induced by polyI:C plus IL-2/IL-12. Similarly, IFN-γ 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-γ 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-β that induce, in an autocrine manner, the production of IFN-γ and thereby highlight that NK cells may control the outcome of protective or injurious immune responses through type I IFN secretion.
- Publication
European Journal of Immunology, 2009, Vol 39, Issue 10, p2877
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200838610