- Human antiviral T cells in tissues
Using a novel human organ donor tissue resource, Gordon et al. reveal how CMV-specific T cells are distributed and function in multiple sites in the context of viral persistence, revealing new insights into immune control of CMV in the body.
- T reg cells with a single TCR
Levine et al. investigate the extent to which regulatory T cells with either a monoclonal T cell receptor (TCR) or random TCR repertoire in place of their developmentally selected specificities maintain TCR-dependent gene expression and immunosuppressive function.
- Myeloid tumor suppressor role for NOL3
Stanley et al. show that loss of Nol3 in mice leads to a myeloproliferative phenotype resembling primary myelofibrosis, with activation of JAK–STAT signaling and significant cellular and molecular resemblance to human disease. These findings provide a novel role for Nol3 in hematopoiesis and myeloid malignancies.
- PID links heparan sulfate to thymopoiesis
Volpi et al. demonstrate that hypomorphic EXTL3 mutations cause abnormalities of heparan sulfate composition, affect signaling in response to growth factors and cytokines, and perturb thymopoiesis, resulting in a novel genetic disease associating skeletal dysplasia, T cell immunodeficiency, and neurodevelopmental delay.
- ERBIN links STAT3 and TGF-β with atopy
Lyons et al. show that STAT3 negatively regulates TGF-β signaling via ERBIN and that cell-intrinsic deregulation of TGF-β pathway activation promotes the IL-4/IL-4Rα/GATA3 axis to support atopic phenotypes in humans.
- Skap2 in integrin activation
Boras et al. demonstrate that Skap2, via interaction with WASp, regulates actin polymerization and binding of talin-1 and kindlin-3 to the β2 integrin, thereby being indispensable for β2 integrin activation and neutrophil recruitment.
- Extrasynaptic NMDA receptor pathological triad
Bading reviews many neurodegenerative diseases sharing heightened extrasynaptic NMDA receptor signaling, which causes a pathological triad with mitochondrial dysfunction, deregulation of transcription, and loss of dendritic structures and connectivity. Areas of therapeutic objects are defined to guide the design of novel neuroprotective combination therapies.
- Regulating TCR hyperresponsiveness in the ZAP-70 W131A mutant mouse
Hsu et al. show that a hypermorphic allele of Zap70, characterized by reduced autoinhibition, is associated with increased TCR signaling and triggers regulatory mechanisms by which negative selection and inhibitory receptors restrain TCR signaling to enforce T cell tolerance.
- Fh1 is essential for HSC functions
Guitart et al. performed an in vivo genetic dissection of the Krebs cycle enzyme fumarate hydratase (Fh1) in the hematopoietic system. Their investigations revealed multifaceted functions of Fh1 in the regulation of hematopoietic stem cell biology and leukemic transformation.
- 27-OH impairs neuronal glucose uptake
Ismail et al. show that 27-hydroxycholesterol, a peripheral cholesterol metabolite capable of passing the blood–brain barrier, reduces brain glucose uptake by upregulating the renin-angiotensin system and inhibiting GLUT4. This alteration affects memory processes and is likely to have implications on neurodegenerative diseases.