The necroptosis adaptor RIPK3 promotes injury-induced cytokine expression and tissue repair.
Journal Article (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
- PMC4220270
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