Domenjó Vila, Eva, 1993-Casella, Valentina, 1991-Iwabuchi, RyutaroFossum, EvenPedragosa Marín, Mireia, 1988-Castellví Fernández, QuimCebollada Rica, PaulaKaisho, TsuneyasuTerahara, KazutakaBocharov, Gennady A.Argilaguet Marqués, Jordi, 1977-Meyerhans, Andreas2023-03-132023-03-132023Domenjo-Vila E, Casella V, Iwabuchi R, Fossum E, Pedragosa M, Castellví Q, Cebollada Rica P, Kaisho T, Terahara K, Bocharov G, Argilaguet J, Meyerhans A. XCR1+ DCs are critical for T cell-mediated immunotherapy of chronic viral infections. Cell Rep. 2023 Feb 14;42(2):112123. DOI: 10.1016/j.celrep.2023.1121232211-1247http://hdl.handle.net/10230/56165The 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.application/pdfeng© 2023 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).XCR1+ DCs are critical for T cell-mediated immunotherapy of chronic viral infectionsinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.celrep.2023.112123CP: ImmunologyFlt3LLCMVSIRPɑ+ DCsT cell exhaustionXCR1+ DCsAnti-PD-L1Chronic infectionImmunotherapyTherapeutic vaccinationinfo:eu-repo/semantics/openAccess