| First Author | Oh J | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 6 | Pages | 1069-77 |
| PubMed ID | 23712430 | Mgi Jnum | J:201198 |
| Mgi Id | MGI:5512783 | Doi | 10.1084/jem.20122695 |
| Citation | Oh J, et al. (2013) MARCH1-mediated MHCII ubiquitination promotes dendritic cell selection of natural regulatory T cells. J Exp Med 210(6):1069-77 |
| abstractText | 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. |
