Mirc11 Disrupts Inflammatory but Not Cytotoxic Responses of NK Cells

Natural killer (NK) cells generate proinflammatory cytokines that are required to contain infections and tumor growth. However, the posttranscriptional mechanisms that regulate NK cell functions are not fully understood. Here, we define the role of the microRNA cluster known as (which includes , and ) in NK cell-mediated proinflammatory responses. Absence of did not alter the development or the antitumor cytotoxicity of NK cells. However, loss of reduced generation of proinflammatory factors and interferon-γ-dependent clearance of or B16F10 melanoma by NK cells. These functional changes resulted from silencing ubiquitin modifiers A20, Cbl-b, and Itch, allowing TRAF6-dependent activation of NF-κB and AP-1. Lack of caused increased translation of A20, Cbl-b, and Itch proteins, resulting in deubiquitylation of scaffolding K63 and addition of degradative K48 moieties on TRAF6. Collectively, our results describe a function of that regulates generation of proinflammatory cytokines from effector lymphocytes.