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Jin Jin Lab,Nature Communications: Mitochondrial dynamics controls antitumor innate immunity by regulating CHIP-IRF1 axis stability


On November 27th, 2017, Dr. Jin’s research group published a research article entitled “Mitochondrial dynamics controls antitumor innate immunity by regulating CHIP-IRF1 axis stability” in Nature Communications.

Innate immune cells including macrophages and dendritic cells are critically involved in host defense against infections and inflammatory responses. Metabolic shifts implied mitochondrial dynamics may involve in Toll-like receptor agonists-mediated inflammatory responses and polarization. However, the role of myeloid immune cells determined by mitochondrial morphology in anti-tumor immunity and the underlying mechanism remains unclear.

In this study, Dr. Jin’s group found that FAM73b, a mitochondrial outer membrane protein serves as a pivotal role in TLRs-regulated mitochondria morphology switching from fusion to fission. Ablation of FAM73b continually causes mitochondrial fission, which specifically promotes IL-12 production. Reverse mitochondria to fission stage in tumor associated macrophages causes T cell activation and profoundly enhances antitumor immune response in multiple tumor models. Mitochondrial morphology affects Parkin expression and recruitment to mitochondria. Parkin controls the stability of the downstream CHIP-IRF1 axis by proteolysis mechanism. These results delineate the mitochondrial dynamics as a potential target for cancer immunotherapy.