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Pulendran and colleagues delineated the mechanisms underlying the nonspecific antiviral effects exerted by the BCG vaccine against SARS-CoV-2 and reveal a pivotal role for BCG-specific CD4+ T cells that produce interferon-γ in imprinting a persistent antiviral innate program in the lung, mediating heterologous viral protection.
Here, the authors show that combining γ9δ2 TCR-mediated metabolic and co-stimulatory stress targeting by chimeric NKG2D or anti-CD277 co-receptors shapes transcriptomic heterogeneity of engineered T cells and is associated with improved control of solid tumors.
Induced pluripotent stem cell (iPSC)-derived macrophages (iMACs) are being used to make chimeric antigen receptor (CAR) macrophages for immunotherapy. Here the authors design a second-generation macrophage-specific CAR by integrating CD3ζ and toll/IL-1R (TIR) domains resulting in an M1-polarized CAR-iMAC with increased antitumor functions.
Wu and colleagues identify gene networks and transcription factors that control the differentiation of stem-like CD8+ CAR T cells into effector or exhausted CD8+ CAR T cells.
Mandal and colleagues report how the chromatin modulator BRWD1 mediates extensive changes in 3D chromatin topology during B cell development by converting static to dynamic cohesin.
Iwawura et al. identify a noncanonical role for NOD1, independent from its CARD-mediated proteoglycan sensing. Interactions between NOD1 and STAT5 are required for optimal lymphopoiesis in response to homeostatic cytokines.
Love and colleagues find an inhibitory function for CD3ζ ITAMs in response to low-affinity ligands, meaning that CD3ζ can perform a dual function in TCR signaling by playing a positive or negative role depending on the affinity of the TCR for its peptide ligand.
Veillette and colleagues show that CD47 on tumor cells interacts in cis with the pro-phagocytic ligand SLAMF7, masking the ability of SLAMF7 to engage its homotypic receptor on macrophages and to trigger phagocytosis.
Luster and colleagues report that lung-resident ST2+ regulatory T cells secrete the IL-1 antagonist IL-1Ra to suppress neutrophils and early innate immune responses to influenza virus infection.
Regulatory T (Treg) cells are functionally heterogeneous, yet how each Treg cell subset exerts its suppressor function remains unresolved. Lin et al. identify IL-27 as a key Treg cell effector molecule selectively required for gut TH17 cell regulation.
Minguet and colleagues systematically examine how individual CD3 chains of the TCR–CD3 complex can improve chimeric antigen receptor (CAR) T cell performance.
Mathis and colleagues identify a subset of muscle mesenchymal stromal cells that coordinates tissue immune responses and drives regenerative mechanisms following muscle injury.
Huot et al. show that interferon-γ (IFN-γ) regulates the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in bronchoalveolar macrophages from cynomolgus macaques up to 18 months postinfection.
Individuals with advanced cancers can develop thrombocytosis and anemia. Huang and colleagues show that in tumor-bearing individuals, increased circulating kynurenine results in megakaryocyte differentiation from megakaryocytic–erythroid progenitor cells by activating the aryl hydrocarbon receptor, resulting in increased expression of RUNX1.
Neutrophils can release S100A8/S100A9 as an alarmin via gasdermin D pores. Here, the authors untangle the regulatory mechanisms driving this pathway and show that active repair processes make these pores transient, which can prevent the usual lytic cell death.
Iliev et al. report that increased Candida albicans accumulation in the mycobiota of patients with severe COVID-19 might be a contributing factor to the immunopathology of severe COVID-19 and have long-lasting effects on the hematopoietic stem cell compartment.
Einav and colleagues characterize peripheral immune blood cells from pediatric patients with severe natural dengue infections. Their findings suggest that disease progression is associated with an inflammatory phenotype accompanied by impaired interferon response, defective antigen presentation and regulation of effector lymphocyte responses.
Liu and colleagues find differential effects of microglial apoE isoforms on brain function and microglial responses. ApoE3 enhances microglial responses, promoting brain function and reducing amyloid deposition and associated neurotoxicity, while the Alzheimer’s disease-associated apoE4 results in lipid droplet accumulation and impaired microglial responses, which are critical for limiting the development of amyloid pathology.
Eisenlohr and colleagues identify a novel influenza A virus peptide that elicits a robust CD8+ T cell response and is restricted by the nonclassical Qa-1 class I molecule.
Here, the authors show that deletion of Pglyrp1 promotes antitumor immunity owing to its inhibitory function in CD8+ T cells and that targeting it can inhibit development of autoimmune neuroinflammation. These findings indicate that PGLYRP1 might be a target for immunotherapy.