Novel non-canonical role of STAT1 in Natural Killer cell cytotoxicity.

ABSTRACT: STAT1 is an important regulator of NK cell maturation and cytotoxicity. Although the consequences of Stat1-deficiency have been described in detail the underlying molecular functions of STAT1 in NK cells are only partially understood. Here, we describe a novel non-canonical role of STAT1 that was unmasked in NK cells expressing a Stat1-Y701F mutant. This mutation prevents JAK-dependent phosphorylation, subsequent nuclear translocation and cytokine-induced transcriptional activity as verified by RNA-seq analysis. As expected Stat1-Y701F mice displayed impaired NK cell maturation comparable to Stat1^-/- animals. In contrast Stat1-Y701F NK cells exerted a significantly enhanced cytotoxicity in vitro and in vivo compared to S

SUBMITTER: Putz EM 

PROVIDER: S-EPMC5048756 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature