RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8+ T cells

N Yatim, H Jusforgues-Saklani, S Orozco, O Schulz… - Science, 2015 - science.org
Science, 2015science.org
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 …
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.
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