XCR1+ DCs are critical for T cell-mediated immunotherapy of chronic viral infections
View/Open
Author
Domenjo-Vila, Eva
Casella, Valentina
Iwabuchi, Ryutaro
Fossum, Even
Pedragosa, Mireia
Castellví, Quim
Cebollada Rica, Paula
Kaisho, Tsuneyasu
Terahara, Kazutaka
Bocharov, Gennady
Meyerhans, Andreas
Publication date
2023-02-14ISSN
2211-1247
Abstract
The contribution of cross-presenting XCR1+ dendritic cells (DCs) and SIRPα+ DCs in maintaining T cell function during exhaustion and immunotherapeutic interventions of chronic infections remains poorly characterized. Using the mouse model of chronic LCMV infection, we found that XCR1+ DCs are more resistant to infection and highly activated compared with SIRPα+ DCs. Exploiting XCR1+ DCs via Flt3L-mediated expansion or XCR1-targeted vaccination notably reinvigorates CD8+ T cells and improves virus control. Upon PD-L1 blockade, XCR1+ DCs are not required for the proliferative burst of progenitor exhausted CD8+ T (TPEX) cells but are indispensable to sustain the functionality of exhausted CD8+ T (TEX) cells. Combining anti-PD-L1 therapy with increased frequency of XCR1+ DCs improves functionality of TPEX and TEX subsets, while increase of SIRPα+ DCs dampened their proliferation. Together, this demonstrates that XCR1+ DCs are crucial for the success of checkpoint inhibitor-based therapies through differential activation of exhausted CD8+ T cell subsets.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
619 - Veterinary science
Pages
29
Publisher
Cell Press
Is part of
Cell Reports
Citation
Domenjo-Vila, Eva, Valentina Casella, Ryutaro Iwabuchi, Even Fossum, Mireia Pedragosa, Quim Castellví, Paula Cebollada Rica, Tsuneyasu Kaisho, Kazutaka Terahara, Gennady Bocharov, Jordi Argilaguet, and Andreas Meyerhans. (2023). XCR1+ DCs are critical for T cell-mediated immunotherapy of chronic viral infections. Cell Reports, 42(2), 112123. doi: 10.1016/j.celrep.2023.112123
Grant agreement number
MICIU-FEDER/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2019-106323RB-I00/ES/Characterization and manipulation of control points of virus infection fates/
MICIU/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I/CEX2018-000792-M/ES/ /
Program
Sanitat Animal
This item appears in the following Collection(s)
- ARTICLES CIENTÍFICS [2555]
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/