Deubiquitinase DUBA is a Post-translational Brake on Interleukin-17 Production in T Cells

Overview

Journal Nature

Specialty Science

Date 2014 Dec 4

PMID 25470037

Citations 80

Authors

Sascha Rutz

Nobuhiko Kayagaki

Qui T Phung

Celine Eidenschenk

Rajkumar Noubade

Xiaoting Wang

Justin Lesch

Rongze Lu

Kim Newton

Oscar W Huang

Andrea G Cochran

Mark Vasser

Benjamin P Fauber

Jason Devoss

Joshua Webster

Lauri Diehl

Zora Modrusan

Donald S Kirkpatrick

Jennie R Lill

Wenjun Ouyang

Vishva M Dixit

Affiliations

Soon will be listed here.

Abstract

T-helper type 17 (TH17) cells that produce the cytokines interleukin-17A (IL-17A) and IL-17F are implicated in the pathogenesis of several autoimmune diseases. The differentiation of TH17 cells is regulated by transcription factors such as RORγt, 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 RORγt in response to TGF-β signalling. Our data identify DUBA as a cell-intrinsic suppressor of IL-17 production.

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