The article focuses on the metabolic vulnerabilities of immune cells involved in allergic airway diseases like asthma. The study investigates how allergen-induced Innate Lymphoid Cells (ILC2s) and T helper type 2 (Th2) cells adapt their metabolism to survive in inflammatory environments. A central finding is that these pathogenic cells rely on cystine-driven glutathione (GSH) synthesis to activate antioxidant systems, specifically GPX4 and TXNRD1, which confer resistance to a type of cell death called ferroptosis by counteracting toxic lipid peroxidation. This redox balance is essential for the cells to acquire and utilize lipids for expansion and function. Ultimately, the research proposes that targeting this metabolic vulnerability, particularly the TXNRD1 system, may be an effective therapeutic strategy to restrain chronic airway inflammation.

References:

• Wientjens C, Doverman M, Zurkovic J, et al. Tolerance to ferroptosis facilitates lipid metabolism and pathogenic type 2 immunity in allergic airway inflammation[J]. Immunity, 2025.

The article details a study on the pathogenesis of systemic rotavirus (RV) infection and biliary atresia (BA) in neonates, highlighting a critical role for the hepcidin-iron axis. The authors, Xu et al., explain that RV infection triggers persistent Type I Interferon (IFN-I) signaling, which upregulates hepcidin in liver macrophages (specifically TREM2+ macrophages) and hepatocytes. This dysregulation impairs iron export, leading to systemic iron overload and subsequent ferroptosis-mediated tissue damage in the liver and intestines. Critically, the study demonstrates that folic acid (FA) supplementation targets this pathway, mitigating liver injury in RV-infected mice and showing promising clinical results—including reduced cholangitis and lower liver transplantation rates—in a clinical trial involving infants with BA.

References:

• Xu Y, Chen X, Fang R, et al. A dysregulated hepcidin-iron axis impairs antiviral immunity and induces lethal liver pathology in neonates[J]. Immunity, 2025.

This article investigates the characteristics and longevity of germinal center T follicular helper (GC-Tfh) cells in non-human primates immunized with an HIV Env protein vaccine. The authors show that an escalating-dose (ED) immunization regimen elicited stronger and more durable GC-Tfh cell responses, which significantly correlated with higher-quality neutralizing antibody titers. Using single-cell RNA sequencing, the study identifies several functionally distinct GC-Tfh subsets, such as IL-4hi and IL-21hi cells, and demonstrates that antigen-specific Tfh clones can persist for over six months without showing signs of exhaustion. Furthermore, the findings reveal that Tfh clones exhibit clonal migration between distal lymph nodes, highlighting a dynamic and widespread immune response critical for sustained humoral immunity.

References:

• Marina-Zárate E, Sutton H J, Lopez P G, et al. Highly functional and prolonged germinal center T follicular helper cell responses are associated with enhanced neutralizing antibody development[J]. Immunity, 2025.

This article examines the molecular regulation of bystander activation in human memory CD8+ T cells that is induced by Interleukin-15 (IL-15). The authors, Lee et al., found that while IL-15 causes these T cells to exhibit NK-like cytotoxicity and elevated expression of markers like NKG2D, concurrent T cell receptor (TCR) signaling suppresses these specific "bystander" features. Mechanistically, this suppression is shown to rely on the Ca²⁺-calcineurin signaling pathway, which activates NFATc1, leading to NFATc1 binding to AP-1 and subsequently limiting the expression of NK-like genes. The study successfully defines an IL-15-specific gene set that characterizes this bystander activation, validating it in memory CD8+ T cells from patients with acute Hepatitis A Virus infection.

References:

• Lee H, Kim S Y, Kim S H, et al. TCR signaling via NFATc1 constrains IL-15-induced bystander activation of human memory CD8+ T cells[J]. Immunity, 2025.

This article investigates the relationship between neuronal hyperactivity and specialized rod-shaped microglia in a mouse model of TDP-43-related neurodegeneration, a condition relevant to Amyotrophic Lateral Sclerosis (ALS). The authors use advanced techniques, including spatial and single-cell RNA sequencing and in vivo calcium imaging, to demonstrate that early cortical hyperactivity induces the formation of these rod-shaped microglia. Crucially, the paper proposes that these specialized microglia interact with neuronal dendrites to remodel inputs, suggesting a neuroprotective role by attenuating cortical excitability. Furthermore, the study identifies the TREM2/DAP12 axis as a regulator for the formation of these protective microglia, linking this signaling pathway to the observed neuroprotection.

References:

• Xie M, Liang Y, Miller A S, et al. Rod-shaped microglia interact with neuronal dendrites to attenuate cortical excitability during TDP-43-related neurodegeneration[J]. Immunity, 2025.

The paper investigates the timing and sequence of events during eukaryogenesis, the origin of eukaryotic cells. The authors use a relaxed molecular clock methodology to date gene duplication events related to key eukaryotic features, particularly those of archaeal and bacterial descent. Their findings suggest that the archaeal host cell was already complex, possessing an elaborated cytoskeleton, endomembrane, and a nucleus/protonucleus, before mitochondrial endosymbiosis occurred. This timeline rejects "mitochondrion-early" models and supports a "complexified-archaeon, late-mitochondrion" sequence, placing the origin of the eukaryotic cell assembly between the Mesoarchaean and the late Palaeoproterozoic eras. The text also details the evolution of specific cellular components, like the cytoskeleton, endomembrane system, and nucleus, based on the calculated ages of their gene duplications.

References:

• Kay, C.J., Spang, A., Szöllősi, G.J. et al. Dated gene duplications elucidate the evolutionary assembly of eukaryotes. Nature (2025). doi.org

The study details how the Tuberous Sclerosis Complex (TSC) proteins regulate the balance of progenitor cells, specifically radial progenitors (RG) and intermediate progenitors (IPs), during neocortex development. The research, primarily using mouse models (TSC1/2 cKO), demonstrates that the loss of TSC proteins shifts this balance toward an increase in IPs, leading to the overproduction and aberrant organization of upper-layer neurons, resulting in cortical expansion and malformations. Furthermore, the study suggests that the evolutionary suppression of TSC protein expression via human-gained enhancers (HGEs), particularly those regulating TSC2, may be a mechanism that facilitated the enhanced generation of neurons necessary for the evolution of the larger human brain. These findings connect the TSC pathway to fundamental mechanisms of cerebral cortex formation and neurodevelopmental disorders such as tuberous sclerosis complex and autism spectrum disorder (ASD).

References:

• Casingal C R, Nakagawa N, Yabuno-Nakagawa K, et al. TSC tunes progenitor balance and upper-layer neuron generation in neocortex[J]. Nature, 2025: 1-11.

The paper describes a breakthrough in modeling primate embryonic development by creating stem cell-derived monkey embryoids that successfully reach the late gastrulation stage (equivalent to Carnegie Stage 8-9). Using an optimized 3D suspension culture system, researchers generated these embryoids from naive pluripotent stem cells and maintained them for up to 25 days, observing key developmental milestones like the formation of the neural plate, primitive gut, and hematopoietic system. Through extensive single-cell transcriptomic analysis and morphological studies, the resulting embryoids were found to largely recapitulate the cell lineage composition and spatial organization of natural monkey embryos. Furthermore, the robust system was validated by CRISPR-Cas9-mediated genetic perturbation of key developmental genes, proving its value as a powerful platform for dissecting early primate development and addressing limitations in traditional embryo research.

References:

• Li J, Li J, Cao J, et al. Modelling late gastrulation in stem cell-derived monkey embryo models[J]. Nature, 2025: 1-12.

The paper presents a comprehensive genomic analysis of 1,364 breast cancers from a Korean cohort (CUBRICS), integrating whole-genome sequencing (WGS) and clinical annotations to characterize the disease landscape. Key findings include the identification of novel driver genes, recurrent gene fusions, and structural variants, suggesting genomic instability emerges decades before tumor diagnosis. The study highlights the utility of WGS-derived features, such as mutational signatures (like those associated with Homologous Recombination Deficiency [HRD]) and tumor heterogeneity scores as potential predictive biomarkers for therapeutic responses to treatments like anti-HER2 and CDK4/6 inhibitors. Furthermore, the researchers investigate focal amplifications (e.g., ERBB2, CCND1, ZNF703) and their mechanisms, showing that absolute copy number, rather than the amplification method (like extrachromosomal DNA), better predicts treatment outcome in HER2-positive cases.

References:

• Kim R, Yu J, Lim J, et al. Whole-genome landscapes of 1,364 breast cancers[J]. Nature, 2025: 1-10.

The paper introduces the concept of the "resistance continuum," a framework explaining how cancer cells gradually adapt to therapy through a dynamic series of cell-state transitions, rather than just immediate genetic mutations. Through longitudinal dose-escalation experiments in various cancer cell lines, researchers demonstrate that resistance is progressively acquired and accompanied by increasing cell fitness. This adaptation involves non-genetic plasticity, including epithelial-to-mesenchymal transition (EMT) as an enabling factor, and the stepwise assembly of new gene expression programs regulated by stress response pathways like NRF2 and ATF4. Crucially, the study identifies that this adaptive process creates metabolic vulnerabilities, suggesting that combining traditional therapy (like the PARP inhibitor olaparib) with targeted inhibitors (like the GLS inhibitor CB-839) can synergistically overcome resistance.

References:

• França, G.S., Baron, M., King, B.R. et al. Cellular adaptation to cancer therapy along a resistance continuum. Nature 631, 876–883 (2024).