Ubc13 maintains the suppressive function of regulatory T cells and prevents their conversion into effector-like T cells

Maintenance of immune homeostasis requires regulatory T (T(reg)) cells. Here we show that T(reg)-specific ablation of Ubc13, a lysine 63-specific ubiquitin-conjugating enzyme, caused aberrant T cell activation and autoimmunity. Although Ubc13 deficiency did not affect T(reg) cell survival or Foxp3 expression, it impaired the in vivo suppressive function of T(reg) cells and rendered them sensitive for acquiring T helper (T(H)) 1- and T(H)17-like effector T cell phenotypes. This function of Ubc13 involved its downstream target, IκB kinase (IKK). The Ubc13-IKK signaling axis controlled the expression specific T(reg) effector molecules, including interleukin 10 (IL-10) and SOCS1. Collectively, these findings suggest that the Ubc13-IKK signaling axis regulates the molecular program that maintains T(reg) function and prevents T(reg) cells from acquiring inflammatory phenotypes.