title: RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8⁺ T cells.
abstract: Dying cells initiate adaptive immunity by providing both antigens and inflammatory stimuli for dendritic cells, which in turn activate CD8(+) T cells through a process called antigen cross-priming. To define how different forms of programmed cell death influence immunity, we established models of necroptosis and apoptosis, in which dying cells are generated by receptor-interacting protein kinase-3 and caspase-8 dimerization, respectively. We found that the release of inflammatory mediators, such as damage-associated molecular patterns, by dying cells was not sufficient for CD8(+) T cell cross-priming. Instead, robust cross-priming required receptor-interacting protein kinase-1 (RIPK1) signaling and nuclear factor κB (NF-κB)-induced transcription within dying cells. Decoupling NF-κB signaling from necroptosis or inflammatory apoptosis reduced priming efficiency and tumor immunity. Our results reveal that coordinated inflammatory and cell death signaling pathways within dying cells orchestrate adaptive immunity.
authors.affiliation: Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, 25 Rue du Docteur Roux, 75015 Paris, France. Institut National de la Santé et de la Recherche Médicale, U818, 25 Rue du Docteur Roux, 75015 Paris, France. Frontières du Vivant Doctoral School, École Doctorale 474, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, 8-10 Rue Charles V, 75004 Paris, France.
authors.forename: Nader
authors.initials: N
authors.lastname: Yatim
authors.affiliation: Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, 25 Rue du Docteur Roux, 75015 Paris, France. Institut National de la Santé et de la Recherche Médicale, U818, 25 Rue du Docteur Roux, 75015 Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Jusforgues-Saklani
authors.affiliation: Department of Immunology, University of Washington, Campus Box 358059, 750 Republican Street, Seattle, WA 98109, USA.
authors.forename: Susana
authors.initials: S
authors.lastname: Orozco
authors.affiliation: Immunobiology Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schulz
authors.affiliation: Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, 25 Rue du Docteur Roux, 75015 Paris, France. Institut National de la Santé et de la Recherche Médicale, U818, 25 Rue du Docteur Roux, 75015 Paris, France.
authors.forename: Rosa
authors.initials: R
authors.lastname: Barreira da Silva
authors.affiliation: Immunobiology Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
authors.affiliation: Department of Immunology, University of Washington, Campus Box 358059, 750 Republican Street, Seattle, WA 98109, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Oberst
authors.affiliation: Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, 25 Rue du Docteur Roux, 75015 Paris, France. Institut National de la Santé et de la Recherche Médicale, U818, 25 Rue du Docteur Roux, 75015 Paris, France.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D053181:Caspase 8 / Q000378:metabolism; D002470:Cell Survival; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D041681:NIH 3T3 Cells; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse; C485615:Ripk3 protein, mouse; D053181:Caspase 8