RIPK1 and NF-?B 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 ?B (NF-?B)-induced transcription within dying cells. Decoupling NF-?B 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.

SUBMITTER: Yatim N 

PROVIDER: S-EPMC4651449 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature