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Immunity. 2014 Oct 16;41(4):567-78. doi: 10.1016/j.immuni.2014.09.016.

The necroptosis adaptor RIPK3 promotes injury-induced cytokine expression and tissue repair.

Author information

1
Department of Pathology, Immunology and Microbiology Program, University of Massachusetts Medical School, Worcester, MA 01655, USA.
2
Department of Pathology, Immunology and Microbiology Program, University of Massachusetts Medical School, Worcester, MA 01655, USA. Electronic address: francis.chan@umassmed.edu.

Abstract

Programmed necrosis or necroptosis is an inflammatory form of cell death that critically requires the receptor-interacting protein kinase 3 (RIPK3). Here we showed that RIPK3 controls a separate, necrosis-independent pathway of inflammation by regulating cytokine expression in dendritic cells (DCs). Ripk3(-/-) bone-marrow-derived dendritic cells (BMDCs) were highly defective in lipopolysaccharide (LPS)-induced expression of inflammatory cytokines. These effects were caused by impaired NF-κB subunit RelB and p50 activation and by impaired caspase 1-mediated processing of interleukin-1β (IL-1β). This DC-specific function of RIPK3 was critical for injury-induced inflammation and tissue repair in response to dextran sodium sulfate (DSS). Ripk3(-/-) mice exhibited an impaired axis of injury-induced IL-1β, IL-23, and IL-22 cytokine cascade, which was partially corrected by adoptive transfer of wild-type DCs, but not Ripk3(-/-) DCs. These results reveal an unexpected function of RIPK3 in NF-κB activation, DC biology, innate inflammatory-cytokine expression, and injury-induced tissue repair.

PMID:
25367573
PMCID:
PMC4220270
DOI:
10.1016/j.immuni.2014.09.016
[Indexed for MEDLINE]
Free PMC Article

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