Format

Send to

Choose Destination
Science. 2015 Oct 16;350(6258):328-34. doi: 10.1126/science.aad0395. Epub 2015 Sep 24.

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

Author information

1
Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, 25 Rue du Docteur Roux, 75015 Paris, France. Institut National de la Santé et de la Recherche Médicale, U818, 25 Rue du Docteur Roux, 75015 Paris, France. Frontières du Vivant Doctoral School, École Doctorale 474, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, 8-10 Rue Charles V, 75004 Paris, France.
2
Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, 25 Rue du Docteur Roux, 75015 Paris, France. Institut National de la Santé et de la Recherche Médicale, U818, 25 Rue du Docteur Roux, 75015 Paris, France.
3
Department of Immunology, University of Washington, Campus Box 358059, 750 Republican Street, Seattle, WA 98109, USA.
4
Immunobiology Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
5
Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.

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.

Comment in

PMID:
26405229
PMCID:
PMC4651449
DOI:
10.1126/science.aad0395
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center