Immunology
Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19COVID-19 still poses a major health threat with worldwide ongoing hospitalizations and mortality. Aberrant antibody responses are a crucial cause of development of severe COVID-19 by inducing hyperinflammation, edema, and thrombus formation. Here, we identified entospletinib as a promising therapeutic candidate against severe COVID-19.
Inhibition of the SREBP pathway prevents SARS-CoV-2 replication and inflammasome activationSARS-CoV-2 exploits host lipid metabolism for its replication and pathogenesis. Blocking SREBPs prevents SARS-CoV-2–induced lipid remodeling, virus replication, cell death, and inflammatory mediators, suggesting SREBP as a potential host-derived antiviral target.
T cell differentiation drives the negative selection of pathogenic mitochondrial DNA variantsFluorescently activated cell-sorting coupled with high-throughput single cell mtDNA sequencing reveals enhanced negative selection of pathogenic mtDNA variants in T cells, with more mature, memory cells exhibiting lower mutation levels than their naïve counterparts.
Convergent evolution and B-cell recirculation in germinal centers in a human lymph nodeThe study characterizes an ongoing immune response by sequencing B-cells from 10 germinal centers and finds diverse clonal patterns and convergent evolution, indicating re-engagement and rediversification of B-cell clones across GCs.
Tumor necrosis factor mediates USE1-independent FAT10ylation under inflammatory conditionsThe finding of TNF-dependent FAT10ylation in the absence of USE1 identifies seven additional, so far unknown FAT10-reactive E2 conjugating enzymes.
High-resolution kinetic characterization of the RIG-I-signaling pathway and the antiviral responseThis study takes a comprehensive approach to understand the dynamics of the cell-intrinsic response towards virus infection and how viruses actively modulate this.
Caspase-4 dimerisation and D289 auto-processing elicit an interleukin-1β-converting enzymeThe noncanonical inflammasome generates p32/p9 and p34/p9 active caspase-4 species via dimerisation and autocleavage; both species cleave GSDMD to induce pyroptosis, whereas p34/p9 matures IL-1β.
Macrophage Sult2b1 promotes pathological neovascularization in age-related macular degenerationSult2b1 deficiency attenuates pathologic neovascularization by inhibiting M2 macrophage polarization and promoting cholesterol efflux via the LXR–ABCA1/G1 pathway.
PASCAR: a multiscale framework to explore the design space of constitutive and inducible CAR T cellsAn experimentally validated protein abundance structured population dynamic model for CAR T cells (PASCAR) that integrates processes from molecules to single cells to cell populations and systematically explores the design space of constitutive and tunable CAR T cells.
Inhibition of protein arginine deiminase 4 prevents inflammation-mediated heart failure in arthritisInhibition of protein arginine deiminase 4 (PAD4), with an orally available inhibitor (JBI-589), prevents the development of hypertrophic cardiomyopathy and diastolic heart failure in murine inflammatory arthritis with reduced neutrophil infiltration, NET deposition, and biomarkers of thromboinflammation in the myocardium.