title: MARCH1-mediated MHCII ubiquitination promotes dendritic cell selection of natural regulatory T cells.
abstract: Membrane-associated RING-CH1 (MARCH1) is an E3 ubiquitin ligase that mediates ubiquitination of MHCII in dendritic cells (DCs). MARCH1-mediated MHCII ubiquitination in DCs is known to regulate MHCII surface expression, thereby controlling DC-mediated T cell activation in vitro. However, its role at steady state or in vivo is not clearly understood. Here, we show that MARCH1 deficiency resulted in a substantial reduction in the number of thymus-derived regulatory T cells (T reg cells) in mice. A specific ablation of MHCII ubiquitination also significantly reduced the number of thymic T reg cells. Indeed, DCs deficient in MARCH1 or MHCII ubiquitination both failed to generate antigen-specific T reg cells in vivo and in vitro, although both exhibited an increased capacity for antigen presentation in parallel with the increased surface MHCII. Thus, MARCH1-mediated MHCII ubiquitination in DCs is required for proper production of naturally occurring T reg cells, suggesting a role in balancing immunogenic and regulatory T cell development.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jaehak
authors.initials: J
authors.lastname: Oh
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.forename: Günther
authors.initials: G
authors.lastname: Baravalle
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cohn
authors.forename: Jessica
authors.initials: J
authors.lastname: Ma
authors.forename: Bryan
authors.initials: B
authors.lastname: Lo
authors.forename: Ira
authors.initials: I
authors.lastname: Mellman
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishido
authors.forename: Mark
authors.initials: M
authors.lastname: Anderson
authors.forename: Jeoung-Sook
authors.initials: JS
authors.lastname: Shin
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000276:immunology* / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C545340:MARCH1 protein, mouse; D044767:Ubiquitin-Protein Ligases