RIPK1 and NF- B signaling in dying cells determines cross-priming of CD8+ T cells - Archive ouverte HAL Access content directly
Journal Articles Science Year : 2015

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

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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.

Dates and versions

pasteur-01380732 , version 1 (13-10-2016)

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N. Yatim, H. Jusforgues-Saklani, S. Orozco, O. Schulz, R. Barreira da Silva, et al.. RIPK1 and NF- B signaling in dying cells determines cross-priming of CD8+ T cells. Science, 2015, 350 (6258), pp.328-334. ⟨10.1126/science.aad0395⟩. ⟨pasteur-01380732⟩
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