Microglia, the tissue macrophages of the central nervous system, use phagocytosis of loosely organized amyloid beta (Aβ) to construct dense-core plaques, one of the defining histopathological features of Alzheimer’s disease. The biology of this process parallels macrophage construction of granulomas in tuberculosis and other settings.
Brief Definitive Reports
In an international cohort of 112 children hospitalized for moderate to critical COVID-19 pneumonia, we identified 12 children with one of four known recessive inborn errors of type I interferon immunity: X-linked TLR7 and autosomal IFNAR1, STAT2, and TYK2 deficiencies.
Technical Advances and Resources
Highly protective antimalarial antibodies via precision library generation and yeast display screening
This study applied innovative antibody screening technologies to discover antimalarial antibody variants with enhanced protective potency. Study authors applied precision DNA library generation, high-throughput screening, and analysis of next generation sequencing data to identify mutations that improved malaria protection following in vivo infectious challenge.
The present study characterizes the 3D anatomy of meningeal lymphatic vasculature and associated CSF drainage by postmortem light-sheet imaging in mice and by real-time magnetic resonance imaging in humans, demonstrating conserved lymphatic circuitries in contact with dural venous sinuses.
Li et al. report the appetite-suppressing effect of a class of commonly prescribed antimigraine drugs in mice and illustrate the underlying neural pathway using a combination of genetic, metabolic, and transcriptomic analyses.
Phostensin, a protein phosphatase 1 regulatory subunit, supports lymphocyte integrin-dependent functions by mediating dephosphorylation of Rap1 to stabilize the MIT complex, thereby enabling the population of peripheral lymphoid organs and T cell–mediated colitis.
Epithelial HNF4A shapes the intraepithelial lymphocyte compartment via direct regulation of immune signaling molecules
The nuclear receptor HNF4A is associated with susceptibility to inflammatory bowel disease. This study identifies the importance of HNF4A in controlling crosstalk between intestinal epithelial cells and intraepithelial lymphocytes. Epithelial HNF4A serves as a transcription factor for immune signaling molecules and promotes the development of natural intraepithelial lymphocytes.
Irradiation induces a loss of HSC function. Pelinski et al. show that this is linked to the loss of H3K9me3 at intronic LINE-1 of HSC genes. They reveal that a TNF-α/NF-κB/H3K9me3/LINE-1 axis maintains HSC gene expression and function independently of DNA damage.
Th17 cells restrain their own pathogenicity by producing IL-24, which induces IL-10 in a cell-intrinsic manner. IL-24 creates a STAT3 sink at the inner mitochondrial membrane and contributes in redirecting STAT3 from the nucleus to the mitochondrial compartment.
Differential IL-12 signaling induces human natural killer cell activating receptor-mediated ligand-specific expansion
Low IL-12 concentrations are sufficient to induce expansion of human NK cells by innate-activating NK receptor-orchestrated differential IL-12 signaling.
Cho et al. describe the antibody immune response after a single dose of the Ad26.COV2.S vaccine compared with mRNA vaccines. They find that Ad26.COV2.S vaccination produces fewer memory B cells but with a potency and breadth comparable to those found after mRNA vaccination.
Zhang et al. identified chemokine CCL17 as a contributor to age-related heart failure in humans and mice via regulating plasticity and differentiation of T cells. Their findings suggested CCL17 as a novel therapeutic target in age-related heart failure.
The study demonstrates that dominant-negative effects of the misfolded HGSNAT variant in the mouse model of mucopolysaccharidosis IIIC are treatable by glucosamine. This suggests that patients affected with mutations causing the enzyme misfolding can potentially benefit from chaperone therapy.