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Antigen presentation in skull bone marrow by hematopoietic stem and progenitor cells induces myelopoiesis and generates CD4⁺ regulatory T cells in a mouse model of ependymoma, promoting immune tolerance. Treatment with anti-GM-CSF antibody has antitumor effects that are augmented by immunotherapy.

The next generation of genetically engineered mouse models of pancreatic cancer involving a new inducible dual-recombinase system that combines Flp-FRT and Cre-loxP.

RELMβ mediates a gut immune–epithelial circuit regulating tolerance to food antigens, offering targetable candidates for the prevention and treatment of food allergies.

Resistance to combination therapies has been reported in rhabdomyosarcoma (RMS). Here, the authors discover that PIK3CA/AKT pathway regulation of multidrug-resistant ABC transporters is involved in the resistance to therapies in RMS, and use of the PI3Kα inhibitor alpelisib re-sensitizes RMS to therapy.

A single-cell transcriptomic analysis of endometriosis, endometriomas, eutopic endometrial samples and uninvolved ovary tissues highlights cell populations characteristic of these tissue types. Transcriptional and cellular heterogeneity across tissues suggests novel therapeutic targets and biomarkers for this disease.

Sensory neurons may regulate innate immune cells, but their roles in humoral immunity is still unclear. Here the authors show that bacterial infection and asthma induction induce sensory neuron production of distinct neurotransmitters to dampen B cell responses but differentially target IgG and IgE, respectively, to specifically modulate the symptoms.

Pilcher et al. present a single-cell transcriptomics-based immune atlas of participants with newly diagnosed multiple myeloma, reporting on the association of cell types, gene expression and intercellular interactions with disease progression phenotypes.

Single-cell RNA-seq analysis is conventionally limited to gene-level quantification, missing transcript diversity. Here, authors present DOLPHIN, a deep learning method that enables exon- and junction-level analysis to improve cell representation and detect alternative splicing.

Chemotherapy induces bone loss that compromises skeletal health in cancer patients. Here, the authors show that chemotherapy-induced senescence in bone marrow adipo-lineage cells leads to bone loss and demonstrate that senolytic targeting of senescent cells preserves skeletal health during chemotherapy, providing a potential strategy to protect the skeleton in cancer therapy.

This multiomic study, including single-nucleus DNA methylation and chromatin conformation matched with single-nuclei RNA sequencing, provides insights into the epigenomic landscape of human subcutaneous adipose tissue.

Several non-haematopoietic-cell-derived cytokines, including interleukin (IL)25, have been implicated in inducing T helper 2 (T_H2) cell-dependent inflammation, but their precise role has been unclear. Here, IL25 is shown to promote the accumulation of multipotent progenitor cells in gut-associated lymphoid tissue. These cells can give rise to macrophage or granulocyte lineages that promote the differentiation of T_H2 cells and contribute to protective immunity against helminth infections.

GBA, a major gene for Parkinson’s disease and dementia with Lewy bodies, is associated with increased risk of developing dementia. Here, we demonstrate that GBA mutations in mice contribute to cognitive deficits through α-synuclein-independent mechanisms that impact synaptic vesicle endocytosis.

In this work, authors show that via CD48–Als6 interaction, eosinophils can kill Candida albicans in vitro and protect against systemic candidiasis in vivo, reducing the fungal growth and improving survival of mice.

Single-cell analysis of patient brains and cortical organoids links disrupted developmental metabolic reprogramming to postnatal synaptic dysfunction in dup15q syndrome, revealing shared neuronal changes with idiopathic autism.

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

This Review provides an update on the role of innate and adaptive immune cells in the pathogenesis of osteoarthritis. The authors discuss emerging therapeutics that target the immune system in osteoarthritis and the challenges that limit the movement towards personalized medicine.

Single-nucleus transcriptomes of frontal cortex and choroid plexus samples from patients with COVID-19 reveal pathological cell states that are similar to those associated with human neurodegenerative diseases and chronic brain disorders.

Basophils are associated mainly with allergy and immune responses to parasites. Mack and colleagues now show that 'antigen-specific' basophils contribute to the humoral memory response by supplying interleukins 4 and 6.

SIDISH integrates single-cell and bulk RNA sequencing data using deep learning to identify high-risk cell populations and prognostic biomarkers, enabling in silico perturbations that could guide precision therapeutics and advance personalized medicine.

Anti-integrin therapy inhibits lymphocyte trafficking in ulcerative colitis. Here Mennillo et al. use single-cell and spatial -omics to show modulation of mononuclear phagocytes and other networks, identifying gene sets related to treatment response.

Immune cells are under evolutionary pressure due to their anti-infective defence role. Here Salvador-Martínez and Murga-Moreno et al. combine population genetics approaches and Human Cell Atlas data, to quantify the adaptation of human immune cell types and suggest high adaptation rates in tissue-resident cells at the frontline of infections.

The fibrotic encapsulation of subcutaneous silicone implants in mice can be suppressed by softening the implant surface or inhibiting the integrin-mediated activation of transforming growth factor beta 1.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Dexamethasone has been used in the treatment of critically ill COVID-19 patients. Here the authors apply transcriptomics to investigate the effects of dexamethasone treatment in COVID-19 patients, and show both systemic and compartment-specific effects.

JWST observed helium and water in the atmosphere of the giant planet WASP-107 b, revealing a vast outflow of gas and evidence for recent inward migration. The findings shed light on how giant planets lose mass and evolve over time.

Methylation and mass cytometry investigations demonstrate the consequences of smoke exposure in humans at the single-cell level.

A chromatin immunoprecipitation and sequencing (ChIP-Seq) data analysis package, QuEST, facilitates transcription factor binding site discovery at about 20-base-pair resolution.

Impaired wound healing that leads to scar remains a clinical challenge. Here, the authors study the effects of hydrogel crosslinking on cellular behavior in skin wounds and its effect on immune and stromal cell activity.

A regional atlas of the ageing human brain—spanning six distinct anatomical regions from individuals with and without Alzheimer’s dementia—provides insights into cellular vulnerability, response and resilience to Alzheimer’s disease pathology

Cabozantinib, an inhibitor of multiple receptor tyrosine kinases, has efficacy in a mouse model of neurofibromatosis type I and has clinical activity in reducing plexiform neurofibroma volume in a phase II trial of patients with NF1.

Renal fibrosis is caused by renal inflammation, although the underlying mechanisms are unclear. Here, the authors discuss the function of tubular epithelial cells and specific leukocytes—including macrophages, CD4⁺T cells and mast cells—in the progression from inflammation to fibrosis, as well as the prevention of fibrosis.

This Resource presents an atlas classifying the age-related changes in human hematopoietic stem and progenitor cells from gestation through aging.

Radke et al. found an interferon response in the brainstem nuclei of acute COVID-19 that, in addition to the inflammatory reaction, spreads throughout the vascular unit altering glial cells and resolves in late disease states in the absence of brain infection.

Aging drives distinct molecular changes in the brain. Here, the authors use scRNAseq and MERFISH and find that in mice, aging induces subtype-specific, regionally biased changes in striatal astrocytes, marked by transcriptional repression, inflammation, and impaired neuronal interactions.