- Proliferation of cells in the HIV reservoir
The latent reservoir for HIV-1 in resting CD4+ T cells prevents cure with antiretroviral therapy. Hosmane et al. provide evidence supporting the hypothesis that a larger fraction of cells in the reservoir is generated by cell proliferation than by direct 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.
- Scg3 as a target for antiangiogenic therapy
LeBlanc et al. uncover secretogranin III (Scg3) as a unique disease-associated vascular permeability and angiogenic factor using comparative ligandomics. Scg3-neutralizing antibodies alleviate vascular leakage in diabetic retinopathy mice and retinal neovascularization in oxygen-induced retinopathy mice with high efficacy.
- 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.
- 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.
- Complement receptor 3 regulates brain Aβ turnover
Czirr et al. report that microglia lacking complement receptor 3 display increased extracellular Aβ degrading activity and that targeting the receptor with a small molecule increases Aβ clearance in vivo, thus identifying a microglial receptor as a novel therapeutic target.