- Deubiquitination of STING by USP21
Chen et al. show that USP21 is a deubiquitinating enzyme for the adaptor protein STING and that it negatively regulates the DNA virus–induced production of type I interferons. HSV-1 infection recruited USP21 to STING at a late stage by p38-mediated phosphorylation of USP21 at Ser538.
- Multiple uracil-repair pathways for A-T SHM
Girelli Zubani et al. show that the Pms2 component of the mismatch repair complex and multiple uracil glycosylases contribute, each with a distinct strand bias, to enlarge the Ig gene mutation spectrum from G-C to A-T bases.
- Eosinophil-derived IL-4 drives heart failure
Diny et al. report a pathogenic role for eosinophils in autoimmune myocarditis and dilated cardiomyopathy. Eosinophils are required for progression of myocarditis to dilated cardiomyopathy and drive severe disease when present in large numbers. Activated cardiac eosinophils mediate this process through IL-4.
- Inflammatory monocytes activate NK cells via IL-18
Although type I interferon is critical for NK cell activation, the underlying mechanism is under debate and is unknown during a mucosal infection. Lee et al. have determined that type I interferon induces inflammatory monocytes to produce IL-18 to directly activate NK cells to combat viral infections.
- Neuropilin 1 in VEGF-induced vascular permeability
Fantin et al. show that the VEGF isoform VEGF165 signals through a complex of VEGFR2 and NRP1, in which the NRP1 cytoplasmic domain promotes the ABL-mediated activation of SRC family kinases to evoke a hyperpermeability response, a known cause of pathological edema.
- Regulation of viral RNA sensors by sumoylation
Hu et al. show that sumoylation of the viral RNA sensors RIG-I and MDA5 by TRIM38 in uninfected and early-infected cells, and their desumoylation by SENP2 in the late phase of infection, ensure efficient innate immune responses to RNA viruses and their timely termination upon resolution of infection.
- PD-L1 on tumor cells suppresses intratumoral CTLs
Both tumor- and host-derived PD-L1 can play critical roles in immunosuppression; differences in tumor immunogenicity appear to underlie their relative contributions. Juneja et al. show that in immunogenic MC38 tumors, PD-L1 on tumor cells dominates in suppressing tumor immunity by inhibiting CD8 T cell cytotoxicity.
- ZMPSTE24 impedes viral infection
Fu et al. show that ZMPSTE24 is a broad-spectrum antiviral protein that inhibits entry of selected fusogenic viruses by functioning as an effector in the IFITM pathway. ZMPSTE24 protease activity is dispensable for viral restriction. In mice, ZMPSTE24 deficiency increases susceptibility to influenza infection.
- Autonomous TNF in monocyte survival
Using in vivo experimentation and an in vitro microfluidic system, Wolf et al. demonstrate that monocytes require low levels of self-made TNF for their survival, both during monopoiesis and under specific immune challenges. They highlight the significance of this autonomous mechanism in a mouse multiple sclerosis model in which TNF-deficient monocytes survive less in the inflamed spinal cord, resulting in delayed disease onset.