| First Author | Moriwaki K | Year | 2014 |
| Journal | Immunity | Volume | 41 |
| Issue | 4 | Pages | 567-78 |
| PubMed ID | 25367573 | Mgi Jnum | J:254663 |
| Mgi Id | MGI:6112444 | Doi | 10.1016/j.immuni.2014.09.016 |
| Citation | Moriwaki K, et al. (2014) The necroptosis adaptor RIPK3 promotes injury-induced cytokine expression and tissue repair. Immunity 41(4):567-78 |
| abstractText | 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-kappaB subunit RelB and p50 activation and by impaired caspase 1-mediated processing of interleukin-1beta (IL-1beta). 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-1beta, 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-kappaB activation, DC biology, innate inflammatory-cytokine expression, and injury-induced tissue repair. |
