The deubiquitinase Otub1 controls the activation of CD8⁺ T cells and NK cells by regulating IL-15-mediated priming.

ABSTRACT: CD8⁺ T cells and natural killer (NK) cells are central cellular components of immune responses against pathogens and cancer, which rely on interleukin (IL)-15 for homeostasis. Here we show that IL-15 also mediates homeostatic priming of CD8⁺ T cells for antigen-stimulated activation, which is controlled by a deubiquitinase, Otub1. IL-15 mediates membrane recruitment of Otub1, which inhibits ubiquitin-dependent activation of AKT, a kinase that is pivotal for T cell activation and metabolism. Otub1 deficiency in mice causes aberrant responses of CD8⁺ T cells to IL-15, rendering naive CD8⁺ T cells hypersensitive to antigen stimulation characterized by enhanced metabolic reprograming and effector functions. Otub1 also controls the maturation and acti

SUBMITTER: Zhou X 

PROVIDER: S-EPMC6588407 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature