August 2016 | Volume 213, No. 9
Brief Definitive Reports
- GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis
Littlewood-Evans et al. demonstrate that extracellular succinate leads to the propagation of inflammatory macrophage activation, providing translational evidence to support the development of GPR91 antagonists for the treatment of rheumatoid arthritis.
- Carbonic anhydrase enzymes regulate mast cell–mediated inflammation
Car enzyme inhibition prevents mast cell responses and inflammation following Trichinella spiralis infection or the induction of food allergy–like disease.
- DNA polymerase ι functions in the generation of tandem mutations during somatic hypermutation of antibody genes
Gearhart and collaborators address the long-standing question of the roles of error-prone DNA polymerases in somatic hypermutation of antibody genes.
- Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83
Work from the Klein lab shows that CD83 supports T cell selection in the thymus by restraining March8-mediated MHCII ubiquitination and internalization.
- Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection
Mintern, Villadangos, and colleagues show that MARCH 8 plays a role in the posttranslational regulation of surface MHC II expression in thymic epithelial cells, with important implications for CD4+ T cell selection.
- BCL-B (BCL2L10) is overexpressed in patients suffering from multiple myeloma (MM) and drives an MM-like disease in transgenic mice
Luciano et al. generate transgenic mice expressing the Bcl-B gene under the control of the VH promoter and Eµ enhancer and show that these mice recapitulate the characteristic features of human MM.
- An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth
Janes et al. developed an anti-ADAM10 mAb (8C7) that binds to an active form of ADAM10 present in tumors, particularly in stem-like cells. Administration of 8C7 inhibits Notch activity and tumor growth in mouse models, including regrowth after chemotherapy.
- Widespread transneuronal propagation of α-synucleinopathy triggered in olfactory bulb mimics prodromal Parkinson’s disease
Rey et al. generate a mouse model for the spatial propagation of α-synuclein pathology that mimics prodromal Parkinson's disease.
- Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ–mediated host defenses
Gay et al. identify a Toxoplasma gondii secreted effector that recruits NuRD transcriptional repressor and blocks IFN-γ–stimulated STAT1-dependent gene expression, thus dampening host responses to infection.
- Blimp-1–mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis
Khan et al. demonstrate that in chronic toxoplasmosis, CD4 T cell–intrinsic expression of Blimp-1 results in progressive exhaustion, which in turn contributes to CD8 T cell exhaustion and poor pathogen control.
- High antigen levels induce an exhausted phenotype in a chronic infection without impairing T cell expansion and survival
Using recombinant antigen variant-expressing chronic LCMV strains, Zehn and colleagues showed that amount rather than antigen strength is a key determinant of inducing a chronic infection phenotype in T cells.
- Inflammatory monocytes and NK cells play a crucial role in DNAM-1–dependent control of cytomegalovirus infection
Jonjic et al. show that inflammatory macrophages play an essential role in the control of murine CMV (MCMV) infection through a DNAM-1–PVR pathway.
- Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza S. aureus pneumonia
Phagocyte oxidative burst is the primary source of lethal lung injury during influenza and MRSA coinfection.
- Multiple allogeneic progenitors in combination function as a unit to support early transient hematopoiesis in transplantation
Combination of multiple units of allogeneic HSPCs exerts radioprotective and bridging effect, allowing single-donor hematopoiesis by a principal graft.
- Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion
Activation of TNFR2 with a novel agonist expands T reg cells in vivo and protects allo-HCT recipients from acute GvHD while sparing antilymphoma and antiinfectious properties of transplanted donor T cells.
- A miR-155–Peli1–c-Rel pathway controls the generation and function of T follicular helper cells
Xiao and collaborators show that miR-155 regulates T follicular helper cell development and function by suppressing the E3 ubiquitin ligase Peli1.
- Orientation-specific RAG activity in chromosomal loop domains contributes to Tcrd V(D)J recombination during T cell development
Zhao and collaborators use linear amplification–mediated high-throughput genome-wide translocation sequencing to examine TCRδ VDJ recombination at an unprecedented resolution.