RNF41 regulates the damage recognition receptor Clec9A and antigen cross-presentation in mouse dendritic cells
- Author(s)
- Tullett, KM; Tan, PS; Park, HY; Schittenhelm, RB; Michael, N; Li, R; Policheni, AN; Gruber, E; Huang, C; Fulcher, AJ; Danne, JC; Czabotar, PE; Wakim, LM; Mintern, JD; Ramm, G; Radford, KJ; Caminschi, I; O'Keeffe, M; Villadangos, JA; Wright, MD; Blewitt, ME; Heath, WR; Shortman, K; Purcell, AW; Nicola, NA; Zhang, JG; Lahoud, MH;
- Journal Title
- Elife
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- eLife Sciences
- Keywords
- *DAMP recognition; *E3 ubiquitin ligase; *antigen presentation; *dendritic cells; *immunology; *inflammation; *mouse; *ubiquitination
- Research Division(s)
- Structural Biology; Epigenetics And Development; Immunology; Blood Cells And Blood Cancer
- PubMed ID
- 33264090
- Publisher's Version
- https://doi.org/10.7554/eLife.63452
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-02-01 12:08:37
Last Modified: 2021-03-03 09:12:47