title: Ubc13 maintains the suppressive function of regulatory T cells and  prevents their conversion into effector-like T cells.
abstract: 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.
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Chang
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Hongbo
authors.initials: H
authors.lastname: Hu
authors.forename: Jin
authors.initials: J
authors.lastname: Jin
authors.forename: Jiayi
authors.initials: J
authors.lastname: Yu
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhou
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wu
authors.forename: Howard M
authors.initials: HM
authors.lastname: Johnson
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Manolis
authors.initials: M
authors.lastname: Pasparakis
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cheng
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D051550:I-kappa B Kinase / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology; D044763:Ubiquitin-Conjugating Enzymes / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10; C514982:Ube2n protein, mouse; D044763:Ubiquitin-Conjugating Enzymes; D051550:I-kappa B Kinase