Distinct Kinase-Independent Role of RIPK3 in CD11c(+) Mononuclear Phagocytes in Cytokine-Induced Tissue Repair

作者：Moriwaki Kenta; Balaji Sakthi; Bertin John; Gough Peter J; Chan Francis Ka Ming^*

来源：Cell Reports, 2017, 18(10): 2441-2451.

DOI：10.1016/j.celrep.2017.02.015

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 inflamma-some and nuclear factor kB (NF-kB) 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-1b 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.

• 出版日期2017-3-7