UMMS Affiliation

Department of Pathology

Date

6-28-2016

Document Type

Article

Disciplines

Cell Biology | Immunopathology

Abstract

Receptor interacting protein kinase 3 (RIPK3) is a crucial inducer of necroptosis. Its activity is controlled by interaction with other signal adaptors through the "RIP homotypic interaction motif" (RHIM). Recent studies revealed a critical function for RIPK3 in the maintenance of epithelial tissue integrity. In mice with genetic deficiency of the apoptosis adaptors FADD or caspase 8, RIPK3 promotes necroptotic cell death of epithelial cells, leading to excessive and lethal inflammation. In contrast, when FADD and caspase 8 functions are intact, RIPK3 serves as a protector of intestinal epithelial integrity by promoting injury-induced wound repair. In the latter case, RIPK3 promotes optimal cytokine expression by cells of hematopoietic origin. Specifically, bone marrow derived dendritic cells (BMDCs) have an obligate requirement for RIPK3 for optimal secretion of mature IL-1beta and other inflammatory cytokines in response to toll-like receptor 4 (TLR4) stimulation. RIPK3 promotes cytokine expression through two complementary mechanisms: NF-kappaB dependent gene transcription and processing of pro-IL-1beta. We propose that RIPK3 functions in different cell compartments to mediate inflammation through distinct mechanisms.

Rights and Permissions

Citation: Front Cell Dev Biol. 2016 Jun 28;4:70. doi: 10.3389/fcell.2016.00070. eCollection 2016. Link to article on publisher's site

DOI of Published Version

10.3389/fcell.2016.00070

Related Resources

Link to Article in PubMed

Keywords

DSS, IL-1β, IL-23, RIPK1, cancer, inflammasome, necroptosis, tissue repair

Journal Title

Frontiers in cell and developmental biology

PubMed ID

27446921

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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