RNF41 regulates the damage recognition receptor Clec9A and antigen cross-presentation in mouse dendritic cells
| Title: | RNF41 regulates the damage recognition receptor Clec9A and antigen cross-presentation in mouse dendritic cells |
|---|---|
| Authors: | Kirsteen M Tullett; Peck Szee Tan; Hae-Young Park; Ralf B Schittenhelm; Nicole Michael; Rong Li; Antonia N Policheni; Emily Gruber; Cheng Huang; Alex J Fulcher; Jillian C Danne; Peter E Czabotar; Linda M Wakim; Justine D Mintern; Georg Ramm; Kristen J Radford; Irina Caminschi; Meredith O'Keeffe; Jose A Villadangos; Mark D Wright; Marnie E Blewitt; William R Heath; Ken Shortman; Anthony W Purcell; Nicos A Nicola; Jian-Guo Zhang; Mireille H Lahoud |
| Source: | eLife, Vol 9 (2020) |
| Publisher Information: | eLife Sciences Publications Ltd, 2020. |
| Publication Year: | 2020 |
| Collection: | LCC:Medicine; LCC:Science; LCC:Biology (General) |
| Subject Terms: | dendritic cells; DAMP recognition; E3 ubiquitin ligase; ubiquitination; antigen presentation; Medicine; Science; Biology (General); QH301-705.5 |
| Description: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/63452; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.63452 |
| Access URL: | https://doaj.org/article/ce7301ac4e2c47ffba46b495f1882e5b |
| Accession Number: | edsdoj.7301ac4e2c47ffba46b495f1882e5b |
| Database: | Directory of Open Access Journals |