New papers on Immunology
90 new papers on immunology in the last 7 days, within Biology. These are the 50 Pipette rates most worth reading, with the main result in the authors' own words.
The best of the week
Perfluorooctane sulfonate directly interacts with IRF3 to attenuate antiviral innate immunity
Together, our results demonstrate that PFOS directly targets IRF3 to impair innate antiviral immunity, thereby enhancing host susceptibility to viral infection at environmental exposure levels.
Peer-reviewed journalReal-world useProgrammed inhibition of an innate immune receptor via de novo designed transmembrane proteins
Our engineering strategy identifies lead synthetic TM proteins that specifically bind TLR4's transmembrane domain and antagonizes NFκB signaling in human cells.
Peer-reviewed journalBold claims, read criticallyClaims a big stepA Community-Driven Single-Cell PBMC Reference Integrating Landmark Datasets Spanning Health and Disease
Here, we present HARP (Human Cell Atlas Reference for PBMCs), an integrated atlas of ~9 million PBMCs from >2,600 donors across 15 studies spanning four continents, encompassing diverse populations, neonates to 97 years, across health and diverse immune-related diseases.
PreprintImmunotherapy restores therapeutic efficacy of fecal microbiome transplants to treat Clostridioides difficile
Lastly, we developed an Il10-mRNA-LNP immunotherapy to boost IL-10 signaling in FMT Non-Responsive mice and demonstrate that Il10-mRNA-LNP administration is sufficient to restore FMT engraftment and subsequent resolution of C. difficile.
PreprintReal-world useA Neutrophil Defensin-VDAC1 Axis Drives Steatotic Liver Disease
These findings link neutrophil innate immunity to hepatocyte mitochondrial dysfunction, recast host-protective HNPs as pathogenic effectors when hepatocyte mitochondria are lipid-burdened, and establish the HNP-VDAC1 axis as a therapeutic target in MASLD.
PreprintReal-world useSelective ablation of dsDNA-specific plasma cells improves lupus nephritis in NZB/W mice
Treated mice showed a sustained reduction of dsDNA-specific antibodies in the serum and a significant improvement in proteinuria, i.e., kidney pathology.
Peer-reviewed journalBold claims, read criticallyReal-world useRadiation therapy synergizes with mRNA vaccination to overcome microglia-mediated suppression of dendritic cell migration and T cell priming in glioblastoma
Importantly, radiation therapy activates cDC1-mediated endogenous immune responses, which synergizes with mRNA vaccination to promote complete and durable immune-mediated tumor regression.
PreprintReal-world useMINFLUX-nanoscopy of hNAIP/NLRC4 inflammasome activation in single human macrophages
MINFLUX-nanoscopy was able to visualise hNAIP at disrupted phagosomes with nanometre resolution, and also revealed the number and organisation of NLRC4 inflammasome discs within a speck, as well as their hNAIP content, for the first time.
PreprintCollateral Immune Cell Signaling Compromises the Efficacy of T-cell Engaging Therapies for Cardiac Fibrosis
Unexpectedly, while FAP targeted bispecific T-cell engaging antibodies (BiTE(R) molecules) effectively eliminate FAP+ fibroblasts from the heart, they surprisingly lead to accelerated deterioration of cardiac function, enhanced remodeling, and increased scar size.
PreprintReal-world useTargeting ZMYND8 unleashes IL-2 signalling to override T cell exhaustion
Here, using in vivo single-cell CRISPR screens of epigenetic factors and IL-2 signalling regulators, we reveal that the chromatin reader ZMYND8 antagonizes IL-2R–STAT5 signals to restrain effector-like states while promoting terminal exhaustion.
Peer-reviewed journalReal-world useMaleic acid adjuvates BCG to induce CD4+CD8+ T cells and sterilize tuberculosis
These findings establish CD4+CD8+ T cells as superior immune effectors against Mtb, a concept that could fundamentally redirect the current paradigm for anti-TB vaccine development.
PreprintBold claims, read criticallyClaims a big stepLymphatic networks enable diversification of B cell responses to vaccines
Thus, lymphatic networks diversify B cell fate, repertoire and affinity selection, and antibody isotype, revealing a programmable axis for tuning humoral immunity through vaccine design.
PreprintReal-world useCell-intrinsic functions of PD-L1 activate autophagy and prevent cytokine-induced apoptosis
Our findings reveal a role for PD-L1 in protecting thyroid tissue from cytokine-mediated stress and suggest that anti-PD-L1 tissue toxicity may reflect both an immune-mediated attack and intrinsic cellular vulnerability.
Peer-reviewed journalReal-world useA lactate-HIF1-VDR positive feedback loop drives protective SPP1+ macrophage differentiation to inhibit schistosomiasis induced liver fibrosis
Here we show that vitamin D receptor (VDR) signaling in macrophages is essential for limiting fibrosis, acting through a previously unrecognized metabolic epigenetic circuit.
PreprintReal-world useA cell death screen identifies macrophage-depleting agents with therapeutic potential
Together, these findings identify small molecule-mediated macrophage depletion as a promising therapeutic strategy and establish an experimental approach to uncover regulators of macrophage survival.
PreprintReal-world useCD55-CD319-CX3CR1 flow cytometry gating strategy recapitulates scRNA-seq-defined memory CD8 T cell subpopulations
To address this limitation, we developed a surface-marker framework based on CD55, CD319, and CX3CR1 that accurately identifies transcriptionally defined human CD8 T cell populations using standard flow cytometry.
PreprintReal-world useExtracellular Granzyme B Promotes Melanocytorrhagy, Melanocyte Senescence and Aberrant Epidermal Differentiation in Vitiligo and Is Therapeutically Targetable
Conclusions Extracellular GzmB promotes depigmentation associated with inducing melanocyte detachment, melanocyte senescence and aberrant keratinocyte differentiation.
PreprintReal-world useSingle-cell immune repertoire atlas maps coordinated circulating adaptive immune states in inflammatory bowel disease
Together, this atlas connects receptor architecture to coordinated systemic immune remodeling, establishes a foundation for repertoire-informed patient stratification, and prioritizes candidate mechanisms of IBD pathogenesis.
PreprintReal-world useElevated procoagulant platelets driven by necroptosis and pyroptosis aggravate pulmonary thrombosis via suppressing monocyte efferocytosis in severe pneumonia
CONCLUSIONS: Necroptosis/pyroptosis-driven procoagulant platelets exacerbate pulmonary thrombosis by suppressing monocyte efferocytosis in a C1qa-dependent manner.
PreprintReal-world useA CD4-CD8 T-cell circuit converts cardiac inflammation into tissue injury
These findings identify a cooperative CD4-CD8 T-cell circuit that governs autoimmune cardiac injury and establish that acquisition of cytotoxic effector function, rather than inflammation alone, determines the transition from immune infiltration to tissue destruction.
PreprintListeriolysin O recruits UBA1 to ubiquitinate NLRP3 and suppress inflammasome defence
Here we identify a ubiquitin-dependent immune-evasion mechanism in which L. monocytogenes uses listeriolysin O (LLO) to destabilise NLRP3.
PreprintLysosomal acid lipase regulates cholesterol metabolism during phagosomal maturation
Here, we identify lysosomal acid lipase (LIPA) as a key cholesterol ester (CE) hydrolase driving cholesterol mobilization during phagosomal maturation.
PreprintReal-world useA transcriptional continuum from clinically normal to lesional skin: Single-cell trajectory analysis of psoriasis
As a result, we identified a coherent, cell-type-resolved continuum of transcriptional states in which endothelial cells, IL20+ keratinocytes (KCs: IL20), and KGF+ keratinocytes (KCs: KGF) undergo trajectory-dependent state transitions.
PreprintKetogenic diet is protective during endotoxin-induced lung injury through the elevation of BHB
Altogether, our findings reveal that the ketogenic diet provides lung protection during endotoxin-induced lung injury through BHB.
PreprintA Bayesian framework reveals heterogeneous and stochastic decision-making in NK cell cytotoxicity
Event-count analysis supported continuous population heterogeneity, while ordered interaction histories revealed that both stable differences in killing propensity and previous encounters shape cytotoxic decisions.
PreprintHistone deacetylase inhibition induces an antitumor IRF8-dependent trained immunity-like status in macrophages
Here, we demonstrate that histone deacetylase inhibitor (HDACi) priming establishes a trained immunity-like state in monocytes/macrophages, conferring potent antitumor effect in multiple models of triple-negative breast cancer (TNBC) in female mice.
Peer-reviewed journalReal-world useCCR5 blockade inhibits menstrual-driven proinflammatory T cell infiltration into the cervicovaginal mucosa of women
These data demonstrate that menstrual-driven proinflammatory CD4 T cell infiltration into the FRT can be inhibited by CCR5 blockade, which may provide an immunomodulatory approach to treating associated diseases and conditions affecting women.
Peer-reviewed journalReal-world usePseudomonas aeruginosa induces the generation of pathogenic IFNγ+Th17 cells that promote lung damage and chronic inflammation in cystic fibrosis
Here we identify two pathogenic Th17 subsets, Th1/17 + and pro-inflammatory Th17 (pTh17) cells, selectively enriched in CF lungs colonized by Pseudomonas aeruginosa .
Peer-reviewed journalReal-world useNeonatal enteric infection disrupts the microbiota–gut–brain axis through pattern recognition receptors and altered neuroimmune signaling
Together, these findings identify IEC NOD-dependent signaling linking early-life enteric infection to enduring gut-brain dysfunction and reveal probiotic-derived muropeptides as candidate therapeutics.
Peer-reviewed journalReal-world useEpOME functionally antagonises prostaglandin signalling in Spodoptera exigua via a specific GPCR conserved across metazoans
Here the authors identify a phylogenetically conserved GPCR in the insect Spodoptera exigua that delivers inhibitory signals to prostaglandin-mediated immunity via binding the ligand EpOME.
Peer-reviewed journalMechanistic Investigation of Reversible Hibernation-Driven Immune Suppression in Thirteen-Lined Ground Squirrels
These findings identified torpor as a coordinated, multi-tiered state of reversible immune suppression, in which hierarchical metabolic and lineage-specific programs conserve energy while preserving essential immune infrastructure for rapid restoration.
PreprintBold claims, read criticallyTRAM promotes Toll-like-receptor-free myddosome signal transduction
Collectively, this work establishes TRAM as a regulator of myddosome maturation and signalling, providing the molecular basis for receptor-free signal transduction.
Peer-reviewed journalComputational design of optimized and preferentially paired human TCR constant regions for improved T cell function
After several screening rounds, we identified a variant, termed structurally enhanced TCR (SET), that exhibited markedly enhanced surface expression, functional avidity, and reduced mispairing.
Peer-reviewed journalReal-world useElevated ozone activates maternal immunity to drive offspring IgG-mediated anaphylaxis through IgG glycosylation alterations
Our study bridges environmental epidemiology, immunology, and glycobiology to suggest how prenatal oxidative stress reprograms offspring immunity, offering insights into developmental origins of allergic diseases.
Peer-reviewed journalBold claims, read criticallyThe RNA modification N6-methyladenosine restrains SIRPα to license myeloid efferocytosis in atherosclerosis
Conclusions: These findings identify the myeloid m6A - SIRP axis as a novel homeostatic regulator of efferocytosis and establish epitranscriptomic remodeling as a crucial layer of macrophage regulation in atherosclerosis.
PreprintHarmine Plus Exendin-4 Enhances Remission of Recent-Onset Type 1 Diabetes Following Anti-CD3 Therapy
Together, these findings demonstrate that H+E promotes {beta}-cell recovery and resilience while reducing {beta}-cell immunogenicity, enabling remission of recent-onset T1D when combined with anti-CD3 therapy.
PreprintReal-world useCD11c+ microglia promote dysfunctional T cell activation in diffuse midline glioma
Together, these findings identify a previously unrecognised CD11 positive; microglia T-cell axis that establishes immune dysfunction in DMG and provide a rationale for combining myeloid- and T cell-targeted immunotherapies.
PreprintStructure-function profiling identifies determinants of TCR-T cell therapeutic efficacy
These findings provide a mechanistic basis and a conceptual framework for the selection and optimization of TCRs for adoptive immunotherapy.
PreprintReal-world useSymmetric Dimethylarginine Modification Drives Shared and Divergent Antigen Reactivity in Lupus
These results establish that anti-SDMA responses are common in SLE, target methylated arginine motifs across self and viral proteins, and serve as markers of active, complement-consuming disease.
PreprintGut complement C1q and C3 interact with Clostridioides difficile spores via CdeM and contribute to pathogenesis.
Together, these findings identify intestinal complement as a previously unrecognized component of the C. difficile spore-host interface and reveal C1q and C3 as modulators of spore epithelial entry, persistence, and recurrent disease.
PreprintNLRP3 inflammasome signaling orchestrates hepatic granuloma organization and protective immunity
Together, our findings identify NLRP3-Caspase-1/11-IL-18 signaling as a mechanism that coordinates the cellular and spatial organization of protective hepatic granulomas, revealing granuloma architecture as a previously unrecognized function of inflammasome-mediated immunity and providing mechanistic insight into host resistance in visceral leishmaniasis, a potentially fatal neglected tropical disease.
PreprintIFN-κ directs antiviral immunity in human skin
Here, we demonstrate that human keratinocytes preemptively protect the skin against virus infection through constitutive production of IFN-kappa (IFN-{kappa}), a poorly studied type I IFN family member.
PreprintMacrophage restriction in Drosophila wounds and tumors via a matrix degradation–moderating protease inhibitor
Here, we show that the conserved glycosylphosphatidylinositol-linked thioester-containing protein Tep3 from Drosophila , the ortholog of human CD109, limits innate immune cell attachment to damaged and transformed epithelia.
Peer-reviewed journalHepatic cholinergic T cell signaling mediates an adaptive response to alcohol-induced liver stress
Together, these findings identify cholinergic T cell signaling, and cholesterol metabolism within CD4 T cells specifically, as a previously unrecognized adaptive response to alcohol-induced liver stress, nominating candidate therapeutic targets for a disease that is marred by critically limited treatment options.
PreprintFrom mice to humans: A multi-omic predictive framework for translational immunology
Translational accuracy depended on stimulus intensity, as infections and injuries engaged conserved signatures, while single-dose vaccination diverged.
PreprintCode availableDual-targeted nanoparticles enable the ex vivo generation of cytotoxic and phagocytic CAR effector cells
These findings establish an adaptable antibody-conjugated LNP-mRNA platform for the ex vivo generation of CAR-T cells and CAR-monocytes.
PreprintReal-world useThymic age and peripheral residence time determine antitumor competence of CD8 + T cells
Together, these findings establish developmental imprinting as an important determinant of CD8 + T cell heterogeneity and identify CXCR3 + IL-18Rα + CD8 + T cells as key effectors for antitumor immunity.
Peer-reviewed journalTREM2 Orchestrates Myeloid Cell Programming and Immune Dysregulation in Pulmonary Hypertension
Conclusions: TREM2 is a novel regulator of myeloid-driven immunosuppression and vascular remodeling in PAH and warrants investigation as a therapeutic target and biomarker.
PreprintSingle-Cell and Spatial Analysis Reveals Retention of FCRL4⁺ Memory B Cells in Pediatric Tonsillar Hypertrophy
Using integrated single cell and spatial profiling of pediatric tonsils in a discovery cohort (n = 45) and independent validation cohort (n = 32), we identify a selective expansion and follicular retention of FCRL4+ memory B cells within the mantle zone of hypertrophic tonsils.
PreprintReal-world useA knockout screening platform for interferon-stimulated genes in respiratory cells identifies LY6E as a dominant antiviral effector against coronaviruses
In addition to demonstrating a key role for LY6E in blocking a variety of HCoVs in small airway epithelial cells, this study establishes a loss-of-function CRISPR-Cas9 screening platform for identification of HCoV antiviral ISGs in respiratory cells.
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