UMMS Affiliation

Department of Pathology

Publication Date

3-7-2017

Document Type

Article

Disciplines

Cell Biology | Cellular and Molecular Physiology | Immunopathology

Abstract

Receptor interacting protein kinase 3 (RIPK3) induces necroptosis, a type of regulated necrosis, through its kinase domain and receptor interacting protein (RIP) homotypic interaction motif (RHIM). In addition, RIPK3 has been shown to regulate NLRP3 inflammasome and nuclear factor kappaB (NF-kappaB) activation. However, the relative contribution of these signaling pathways to RIPK3-dependent inflammation in distinct immune effectors is unknown. To investigate these questions, we generated RIPK3-GFP reporter mice. We found that colonic CD11c+CD11b+CD14+ mononuclear phagocytes (MNPs) expressed the highest level of RIPK3 in the lamina propria. Consequently, deletion of the RIPK3 RHIM in CD11c+ cells alone was sufficient to impair dextran sodium sulfate (DSS)-induced interleukin (IL)-23 and IL-1beta expression, leading to severe intestinal inflammation. In contrast, mice expressing kinase inactive RIPK3 were not hypersensitive to DSS. Thus, a key physiological function of RIPK3 is to promote reparative cytokine expression through intestinal CD11c+ MNPs in a kinase- and necroptosis-independent manner.

Keywords

IL-1b, IL-23, RHIM, RIPK3, colitis, dextran sodium sulfate, inflammation, injury, necroptosis, tissue repair

Rights and Permissions

Copyright 2017 The Author(s)

DOI of Published Version

10.1016/j.celrep.2017.02.015

Source

Cell Rep. 2017 Mar 7;18(10):2441-2451. doi: 10.1016/j.celrep.2017.02.015. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID

28273458

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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