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Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

PU.1^low CD28-expressing microglia may act as suppressive cells in Alzheimer’s disease, mitigating its progression by reducing neuroinflammation and amyloid plaque load, indicating potential immunotherapeutic approaches for treatment.

In a mouse model, maternal obesity during pregnancy can lead to fatty liver disease in the offspring, driven by aberrant developmental programming of Kuppfer cells.

Mutations in the Hedgehog signaling have not been previously associated to diabetes. Here, authors identify a missense variant of GLI2 in a family with early-onset diabetes and report an essential role of this gene during human iPSC-based pancreatic differentiation.

Vanni et al. show a role for microtubules in YAP/TAZ mechanosignalling. Mechanoresponsive microtubule reorganization into centrosomal arrays allows for AMOT delivery to pericentrosomal proteasomes and degradation, leading to YAP/TAZ activation.

Malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, in turn resulting in delayed mitosis and catastrophic cell division.

The presence of peritoneal metastasis in pancreatic cancers is associated with poor prognosis. Here the authors show that hyaluronan and proteoglycan link protein-1 (HAPLN1) promotes tumour cell plasticity and pro-tumoral immune microenvironment to facilitate peritoneal dissemination in pancreatic cancers.

In a case series of five children with treatment-refractory neuroblastoma, it was feasible to manufacture and administer donor-derived GD2-specific CAR T cells and clinical responses were seen in four patients.

Response to immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) remains suboptimal, even for tumors with elevated tumor mutational burden. Here the authors generate a model of NSCLC with enhanced mutational load, showing that, while still resistant to ICIs, hypermutated tumors become sensitive to dendritic cell-targeted therapy.

Here, the authors show how in β-thalassemia, a perturbed bone marrow microenvironment leads to altered hematopoiesis. Reduced TGFβ reduces autophagy levels, in turn reducing dormancy and priming of haematopoietic stem cells and multipotent progenitors towards erythroid lineage.

Current vaccine strategies for SARS-CoV-2 focus on eliciting neutralising antibodies to the spike protein (S), but differences in immunogenicity of full-length S versus receptor binding domain (RBD) only aren’t fully understood. Here, the authors show immunogenicity of different prime-boost strategies with S and/or RBD in mice and macaques.

Analyses of single-cell transcriptomic data from patients with VEXAS syndrome combined with xenotransplantation experiments in a mouse model of the disease provide insights on the mechanisms of clonal dominance of mutated cells leading to bone marrow failure

Single-cell RNA-seq and CITE-seq were used to profile the glioblastoma immune landscape in humans and mice, revealing the diversity and dynamics of tumor macrophages as the disease progresses from initial diagnosis to recurrence.

Relapse within acute myeloid leukaemia may be driven by the presence of leukaemia stem cells. Here, the authors use single cell RNA-seq seq to characterise leukemia stem cells, and show miR-126 as a potential marker of resistance.

This article describes a mechanism through which CD4⁺ T cells can eradicate MHC-deficient tumours that escape direct CD8⁺ T cell targeting and thereby complement the activity of CD8⁺ T cells and natural killer cells to advance cancer immunotherapies.

The strength and duration of interleukin-2 (IL-2) signals is known to regulate T cell memory. Here the authors show that T cell receptor signalling strength controls the requirement for IL-2 signals to form CD8⁺ T cell memory with high functional activity and a wide range of genes with open chromatin regions.

Scala et al. show that mobilized peripheral blood hematopoietic stem/progenitor cells are more enriched in repopulating stem cells than bone marrow. Moreover, the quantity and type of infused subsets correlated with gene therapy outcome in humans.

Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

IL-12 and IL-23 share the common p40 subunit yet have distinct immunological functions with IL-12 typically contributing to Th1 responses and IL-23 to Th17 responses. Here the authors show that current p40 based therapies for psoriasis are counterproductive owing to an IFN-γ-independent tissue protective function of IL-12 in skin.

An analog optical computer that combines analog electronics, three-dimensional optics, and an iterative architecture accelerates artificial intelligence inference and combinatorial optimization in a single platform, paving a promising path for faster and sustainable computing.

Lamin A/C protects alveolar macrophages against nuclear envelope rupture and DNA damage, but it erodes during aging. Lack of lamin A/C leads to senescence and an aging signature, resulting in vulnerability to influenza virus and lung cancer growth.

iFlpMosaics are a compendium of mouse lines and genetic tools for tissue-agnostic generation and analysis of genetic mosaics.

Interactions between programmed death ligand 2 (PD-L2) and its binding partner RGMb are downregulated by the gut microbiota, a mechanism that may be exploited to enhance the efficacy of PD-1-based cancer immunotherapies.

GPR25 and its ligand define the core chemoaffinity axis GPR25–CXCL17 of the integrated extraintestinal mucosal immune system, regulating how immune responses disseminate to non-intestinal barrier tissues and with implications for understanding and manipulating immunity and inflammation.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

Computational modelling and mouse genetics approaches show that multipotent progenitor cells that have the potential to populate the hepato-pancreato-biliary lineage tree persist in the pancreato-biliary organ rudiment.

Mutations in the RRAGD gene are causative of an autosomal dominant disorder characterized by kidney tubulopathy and cardiomyopathy. Here, the authors identify a new RRAGD P88L mutation, demonstrating that all the identified RRAGD mutations inhibit the nuclear translocation of MiT/TFE transcription factors, resulting in defective responses to lysosomal or mitochondrial damage.

Resident macrophages of the muscularis externa refine the enteric nervous system (ENS) early in life by pruning synapses and phagocytosing enteric neurons, and later switch to a neuro-supportive function, indicating that the ENS is governed by a dedicated population of resident macrophages that adapt to the timely needs of the ENS.

SARS-CoV-2 vaccines and infection induce antibody responses but the evolution of subsequent variants has resulted in the development of escape mutants. Here the authors characterise, at single cell level, the antibody response in donors after a third dose of SARS-CoV-2 mRNA vaccination and show difference in breadth, neutralisation and molecular signature according to the vaccination regimen used.

Electrical activity in neural organoids is captured with a device inspired by a paper-cutting art.

Liver and pancreas cells arise from a common endoderm progenitor in the embryo, but what regulates their cell fate is unclear. Here, the authors show that expression of the Three-Amino-acid-Loop-Extension (TALE) homeobox TG-interacting factor 2 (TGIF2) in hepatocytes reprogrammes the cells to a pancreatic fate.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.

Acquisition of dying tumor cell-associated antigens is an essential step for the initiation of anti-tumor immune response by conventional type 1 dendritic cells (cDC1). Here the authors show that the loss of TIM4 expression in lung tumor associated cDC1 is associated with less efficient uptake of cell associated antigens and reduction of CD8 + T cell activation in advanced lung tumors.

Single-cell-level analysis of memory B cells and their response to vaccination against all SARS-CoV-2 variants of concern in individuals who either had or had not been previously exposed to the virus.

Longitudinal analyses are needed to show how the immune response to Sars-Cov-2 infection changes over time. Here, the authors use multiple strategies to profile the change in immune cell responses from patients with convalescent COVID-19 over the course of ~5 months, showing that although neutralizing antibody responses drop off after ~4 months, B cell immune responses strengthen.

The components of the tumour microenvironment contribute to prostate cancer initiation and progression. Here the authors perform single-cell RNA sequencing and spatial transcriptomics analysis of prostate cancer stroma from mouse models at different stages of the disease and develop a gene signature to predict distant metastasis in patients.

High mitogenic stimuli have been suggested to promote endothelial cell proliferation and sprouting during angiogenesis. Here Pontes-Quero et al., by interfering with levels of VEGF and Notch signalling in single endothelial cells in vivo, find that high mitogenic stimuli instead arrest angiogenesis due to a bell-shaped dose-response to VEGF and MAPK activity that is counteracted by Notch and p21.

The Cre-Lox system allows high spatiotemporal control of genetic modifications. Here the authors present iSuRe-Cre that significantly increases Cre activity in reporter expressing cells, which ultimately increases the efficiency and reliability of Cre-dependent reporter and gene function analysis.

Greter and colleagues identify a population of CD11c⁺F4/80⁺CD64⁺MHCII⁺CX3CR1⁺ macrophages in the mouse mammary gland that is induced by lactation and resembles several subsets of macrophages detected in human milk.

Alveolar macrophages (AM) in the lungs maintain surfactant during homeostasis and respond to infectious pathogens. Here the authors show that in the absence of NKR-P1B, pneumococcal infection is more severe because KO AM have increased rates of lipid surfactant uptake and reduced anti-microbial function.

Here, using single-cell omics and genomic barcoding, the authors identify transcriptional states and DNA accessibility profiles linked to tumour initiation and drug tolerance, highlighting the complexity of cancer. This study suggests that cancer evolution is driven by pre-encoded factors.

Serum Amyloid P is a humoral component with established roles in the response to bacterial infection and regulation of tissue remodeling. Here the authors provide evidence to a further crucial role of serum amyloid P in the context of fungal pathogen Aspergillus fumigatus.

3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.

Transcriptomic, proteomic and immune repertoire profiling reveals distinct peripheral features of MIS-C and pediatric COVID-19, including elevated soluble spike protein levels, more pronounced type II IFN-dependent gene expression and a higher B cell mutation rate in patients with MIS-C.

In a cohort of recovered patients with COVID-19, virus spike-specific antibodies were consistently elicited, but neutralizing activity was highly variable and inversely correlated with the proportion of CCR6⁺CXCR3⁻ spike-specific circulating follicular helper T cells.

Pericytes are perivascular cells essential for blood-brain barrier maintenance. Here Diéguez-Hurtado et al. show that depletion of the transcription factor RBPJ in pericytes affects their molecular identity and disturbs endothelial cell behaviour, inducing the formation of vascular lesions in the brain.

Cell cycle arrest after DNA damage is achieved by the expression of the CDK inhibitor p21. Here the authors show that spontaneous DNA damage incurred in unperturbed cell cycles, leads to cell populations exhibiting a bistable state, with p53 and p21 regulating the proliferation-quiescence decision.