| First Author | Tullett KM | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 33264090 | Mgi Jnum | J:308600 |
| Mgi Id | MGI:6714536 | Doi | 10.7554/eLife.63452 |
| Citation | Tullett KM, et al. (2020) RNF41 regulates the damage recognition receptor Clec9A and antigen cross-presentation in mouse dendritic cells. Elife 9:e63452 |
| abstractText | The dendritic cell receptor Clec9A facilitates processing of dead cell-derived antigens for cross-presentation and the induction of effective CD8(+) T cell immune responses. Here, we show that this process is regulated by E3 ubiquitin ligase RNF41 and define a new ubiquitin-mediated mechanism for regulation of Clec9A, reflecting the unique properties of Clec9A as a receptor specialized for delivery of antigens for cross-presentation. We reveal RNF41 is a negative regulator of Clec9A and the cross-presentation of dead cell-derived antigens by mouse dendritic cells. Intriguingly, RNF41 regulates the downstream fate of Clec9A by directly binding and ubiquitinating the extracellular domains of Clec9A. At steady-state, RNF41 ubiquitination of Clec9A facilitates interactions with ER-associated proteins and degradation machinery to control Clec9A levels. However, Clec9A interactions are altered following dead cell uptake to favor antigen presentation. These findings provide important insights into antigen cross-presentation and have implications for development of approaches to modulate immune responses. |
