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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Moriwaki, K; Balaji, S; McQuade, T; Malhotra, N; Kang, J; Chan, FK-M

Published Date

  • October 16, 2014

Published In

Volume / Issue

  • 41 / 4

Start / End Page

  • 567 - 578

PubMed ID

  • 25367573

Pubmed Central ID

  • 25367573

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2014.09.016

Language

  • eng

Conference Location

  • United States