RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8+ T cells
journal contributionposted on 23.09.2020 by Nader Yatim, Hélène Jusforgues-Saklani, Susana Orozco, Oliver Schulz, Rosa Barreira da Silva, Caetano Reis e Sousa, Douglas R Green, Andrew Oberst, Matthew L Albert
Any type of content formally published in an academic journal, usually following a peer-review process.
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.