Department of Pathology
Cell Biology | Cellular and Molecular Physiology | Immunopathology
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.
IL-1b, IL-23, RHIM, RIPK3, colitis, dextran sodium sulfate, inflammation, injury, necroptosis, tissue repair
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DOI of Published Version
Cell Rep. 2017 Mar 7;18(10):2441-2451. doi: 10.1016/j.celrep.2017.02.015. Link to article on publisher's site
Moriwaki K, Balaji S, Bertin J, Gough PJ, Chan FK. (2017). Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair. Open Access Articles. https://doi.org/10.1016/j.celrep.2017.02.015. Retrieved from https://escholarship.umassmed.edu/oapubs/3120
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