Deubiquitinase DUBA is a post-translational brake on interleukin-17 production in T cells

helper type 17 (T(H)17) cells that produce the cytokines interleukin-17A (IL-17A) and IL-17F are implicated in the pathogenesis of several autoimmune diseases(1,2). The differentiation of T(H)17 cells is regulated by transcription factors such as ROR gamma t(3,4), but post-translational mechanisms preventing the rampant production of pro-inflammatory IL-17A have received less attention. Here we show that the deubiquitylating enzyme DUBA is a negative regulator of IL-17A production in T cells. Mice with DUBA-deficient T cells developed exacerbated inflammation in the small intestine after challenge with anti-CD3 antibodies. DUBA interacted with the ubiquitin ligase UBR5, which suppressed DUBA abundance in naive T cells. DUBA accumulated in activated T cells and stabilized UBR5, which then ubiquitylated ROR gamma t inresponse toTGF-beta signalling. Our data identify DUBA as a cell-intrinsic suppressor of IL-17 production.