The maintenance of immune homeostasis requires regulatory T cells (Treg cells). Here we found that Treg cell–specific ablation of Ubc13, a Lys63 (K63)-specific ubiquitin-conjugating enzyme, caused aberrant T cell activation and autoimmunity. Although Ubc13 deficiency did not affect the survival of Treg cells or expression of the transcription factor Foxp3, it impaired the in vivo suppressive function of Treg cells and rendered them sensitive to the acquisition of T helper type 1 (TH1) cell– and interleukin 17 (IL-17)-producing helper T (TH17) cell–like effector phenotypes. This function of Ubc13 involved its downstream target, the kinase IKK. The Ubc13-IKK signaling axis controlled the expression of specific Treg cell effector molecules, including IL-10 and SOCS1. Collectively, our findings suggest that the Ubc13-IKK signaling axis regulates the molecular program that maintains Treg cell function and prevents Treg cells from acquiring inflammatory phenotypes.
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We thank M. Karin (University of California, San Diego) for the IKK2(CA) expression vector; T. Kishimoto (Osaka University) for the mouse Socs1-luc reporter; and personnel from the flow cytometry, DNA analysis, and histology core facilities at MD Anderson Cancer Center for technical assistance. This work is supported by the US National Institutes of Health (AI057555, AI064639 and GM84459) and the G.S. Hogan Gastrointestinal Cancer Research Fund.
The authors declare no competing financial interests.
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Chang, JH., Xiao, Y., Hu, H. et al. Ubc13 maintains the suppressive function of regulatory T cells and prevents their conversion into effector-like T cells. Nat Immunol 13, 481–490 (2012). https://doi.org/10.1038/ni.2267
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