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

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-?B subunit RelB and p50 activation and by impaired caspase 1-mediated processing of interleukin-1? (IL-1?). 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-1?, 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-?B activation, DC biology, innate inflammatory-cytokine expression, and injury-induced tissue repair.

SUBMITTER: Moriwaki K 

PROVIDER: S-EPMC4220270 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature