Author: Madera, Sharline; Rapp, Moritz; Firth, Matthew A.; Beilke, Joshua N.; Lanier, Lewis L.; Sun, Joseph C.
Title: Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide Document date: 2016_2_8
ID: qkdni38b_20
Snippet: We previously demonstrated that the proinflammatory cytokine IL-12 and downstream signaling components STAT4 and Zbtb32 are critical for the clonal-like proliferation of Ly49H + NK cells during MCMV infection (Sun et al., 2012; Beaulieu et al., 2014) . Interestingly, the expansion defect in Ifnar −/− NK cells is nearly as pronounced as that of the Il12rb −/− NK cells, demonstrating a nonredundant role for these cytokines in promoting NK c.....
Document: We previously demonstrated that the proinflammatory cytokine IL-12 and downstream signaling components STAT4 and Zbtb32 are critical for the clonal-like proliferation of Ly49H + NK cells during MCMV infection (Sun et al., 2012; Beaulieu et al., 2014) . Interestingly, the expansion defect in Ifnar −/− NK cells is nearly as pronounced as that of the Il12rb −/− NK cells, demonstrating a nonredundant role for these cytokines in promoting NK cell expansion. Based on our current findings, we propose a complementary role for IL-12 and type I IFN in simultaneously driving cellular proliferation and protecting against cell death via fratricide, respectively, during virus-specific NK cell expansion. Given the use of type I IFN in the clinic and its potential impact in vaccination strategies, it is important to elucidate the direct and indirect roles IFN has on specific cellular compartments during the immune response. Our work brings us one step closer by uncovering a novel protective role of type I IFN signaling in NK cells during viral infection.
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