title: Protein SUMOylation Is Required for Regulatory T Cell Expansion and Function.
abstract: Foxp3-expressing regulatory T (Treg) cells are essential for immune tolerance; however, the molecular mechanisms underlying Treg cell expansion and function are still not well understood. SUMOylation is a protein post-translational modification characterized by covalent attachment of SUMO moieties to lysines. UBC9 is the only E2 conjugating enzyme involved in this process, and loss of UBC9 completely abolishes the SUMOylation pathway. Here, we report that selective deletion of Ubc9 within the Treg lineage results in fatal early-onset autoimmunity similar to Foxp3 mutant mice. Ubc9-deficient Treg cells exhibit severe defects in TCR-driven homeostatic proliferation, accompanied by impaired activation and compromised suppressor function. Importantly, TCR ligation enhanced SUMOylation of IRF4, a critical regulator of Treg cell function downstream of TCR signals, which regulates its stability in Treg cells. Our data thus have demonstrated an essential role of SUMOylation in the expansion and function of Treg cells.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ding
authors.affiliation: Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Aibo
authors.initials: A
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Ma
authors.affiliation: Nuclear Organization and Oncogenesis Unit, INSERM U993, Institut Pasteur, 75015 Paris, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Demarque
authors.affiliation: Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Xin
authors.affiliation: Nuclear Organization and Oncogenesis Unit, INSERM U993, Institut Pasteur, 75015 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dejean
authors.affiliation: Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: chendong@tsinghua.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D058207:Sumoylation / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism* / Q000502:physiology*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D008239:Lysine