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

RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8⁺ T cells
Author: 
Andrew A. Oberst, Ph.D.
Published: 
Oct 2015
Publisher: 
Science.

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.

Copyright © 2015, American Association for the Advancement of Science.

PMID: 26405229 [PubMed - indexed for MEDLINE]
PMCID: PMC4651449 [Available on 2016-10-16]