PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Eosinophils”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

IL-33 Drives Inflammatory Changes and Extracellular Trap Formation in Eosinophils Involving Oxidised LDL and Complement Pathways.

BACKGROUND: IL-33 levels are elevated in the airways of patients with eosinophilic diseases, and IL-33 receptor expression on eosinophils is upregulated in type 2-high environments. However, the role of IL-33 in the regulation of human eosinophils remains unclear. OBJECTIVE: To elucidate the inflammatory effects of IL-33 on the cellular function of human eosinophils. METHODS: Blood eosinophils were stimulated with IL-33, TNF-α, oxidised low-density lipoprotein (oxLDL) and complement fragments (C3a and C5a). Multi-omics analyses, including transcriptomics and proteomics, were performed. Extracellular trap formation (ETosis) was assessed by SYTOX nucleic acid staining and was visualised by immunofluorescence and transmission electron microscopy. RESULTS: Multi-omics analyses revealed an IL-33- and TNF-α-induced inflammatory gene signature characterised by the upregulation of cell surface markers (oxLDL receptor 1, CD22, CD4 and ICAM-1) and inflammatory mediators (C3, CCL3/4 and IL1A/B). CD22 upregulation was specific to IL-33 stimulation. Eosinophils derived from nasal polyps exhibited a gene expression profile similar to that of IL-33-stimulated eosinophils. Functional assays demonstrated that oxLDL and complement fragments differentially prolonged eosinophil survival and altered the expression of adhesion molecules. OxLDL- and complement fragment-induced gene signatures were partly detected in eosinophils derived from nasal polyps. Furthermore, IL-33 triggered ETosis via NADPH oxidase, mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. CONCLUSIONS: IL-33, in conjunction with oxLDL and the complement cascade, induces inflammatory changes in eosinophils, promoting an ETosis-prone phenotype. These pathways represent potential therapeutic targets in refractory eosinophilic diseases.

Humans↗
PubMed1975

The selective eosinophil chemotactic activity of histamine.

Histamine diphosphate was shown to selectively attract human eosinophils from mixed granulocyte populations when over 20% eosinophils were used in a modified Boyden chamber chemotactic assay system. This effect of histamine is abolished by incubation with diamine oxidase (histaminase) and was generated by decarboxylation of L-histidine. A linear dose dependent increase in eosinophil migration was observed between 3 X 10(-7) M and 1.25 X 10(-6) M, while higher concentrations of histamine inhibited the migration of eosinophils. The attractant activity of histamine was not inhibited by H-1 or H-2 receptor antagonists, however, the inhibition of migration observed at higher histamine concentrations was reversed by metiamine, an H-2 receptor antagonist. The effects of histamine upon eosinophil migration were demonstrable using three different assays: (a) counting cells that had traversed 5-mum pore, 12-mum thick polycarbonate filters, (b) counting cells that had migrated various distances into a 3-mum pore, 145-mum cellulose nitrate filters, or (c) measuring the number of cells that had traversed an upper polycarbonate filter and migrated into a lower cellulose nitrate filter using 15Cr-labeled cells. The ability of histamine to enhance eosinophil migration was shown to be dependent upon the presence of a concentration gradient; histamine did not cause a dose-dependent increase in random motility. Furthermore, preincubation of the eosinophils with histamine deactivate the cells to further stimulation by histamine or by C5a. It is concluded that in low doses histamine is a chemoattractant for human eosinophils, while in higher doses histamine inhibits eosinophil migration. These observations may relate to the influx and localization of eosinophils in immediate hypersensitivity reactions.

Amine Oxidase (Copper-Containing)↗
PubMed2023

Intratumor childhood vaccine-specific CD4+ T-cell recall coordinates antitumor CD8+ T cells and eosinophils.

BACKGROUND: Antitumor mechanisms of CD4+ T cells remain crudely defined, and means to effectively harness CD4+ T-cell help for cancer immunotherapy are lacking. Pre-existing memory CD4+ T cells hold potential to be leveraged for this purpose. Moreover, the role of pre-existing immunity in virotherapy, particularly recombinant poliovirus immunotherapy where childhood polio vaccine specific immunity is ubiquitous, remains unclear. Here we tested the hypothesis that childhood vaccine-specific memory T cells mediate antitumor immunotherapy and contribute to the antitumor efficacy of polio virotherapy. METHODS: The impact of polio immunization on polio virotherapy, and the antitumor effects of polio and tetanus recall were tested in syngeneic murine melanoma and breast cancer models. CD8+ T-cell and B-cell knockout, CD4+ T-cell depletion, CD4+ T-cell adoptive transfer, CD40L blockade, assessments of antitumor T-cell immunity, and eosinophil depletion defined antitumor mechanisms of recall antigens. Pan-cancer transcriptome data sets and polio virotherapy clinical trial correlates were used to assess the relevance of these findings in humans. RESULTS: Prior vaccination against poliovirus substantially bolstered the antitumor efficacy of polio virotherapy in mice, and intratumor recall of poliovirus or tetanus immunity delayed tumor growth. Intratumor recall antigens augmented antitumor T-cell function, caused marked tumor infiltration of type 2 innate lymphoid cells and eosinophils, and decreased proportions of regulatory T cells (Tregs). Antitumor effects of recall antigens were mediated by CD4+ T cells, limited by B cells, independent of CD40L, and dependent on eosinophils and CD8+ T cells. An inverse relationship between eosinophil and Treg signatures was observed across The Cancer Genome Atlas (TCGA) cancer types, and eosinophil depletion prevented Treg reductions after polio recall. Pretreatment polio neutralizing antibody titers were higher in patients living longer, and eosinophil levels increased in the majority of patients, after polio virotherapy. CONCLUSION: Pre-existing anti-polio immunity contributes to the antitumor efficacy of polio virotherapy. This work defines cancer immunotherapy potential of childhood vaccines, reveals their utility to engage CD4+ T-cell help for antitumor CD8+ T cells, and implicates eosinophils as antitumor effectors of CD4+ T cells.

Mice↗
PubMed1976

Isolation of human eosinophil phospholipase D.

Phospholipase D preferentially contained in human eosinophil polymorphonuclear leukocytes as compared to other leukocytes was isolated by sequential asion and cation exchange chromatography and gel filtration. The purified eosinophil enzyme specifically liberated choline from I-alpha-phosphatidyl choline with a pH optimum of 4.5-6.0 and exhibited a pI of 5.8-6.2 on polyacrylamide-gel isoelectric focusing, which are properties shared by phospholipase D from plant sources; however, its apparent mol wt of 60,000 is approximately one-half that of the plant enzymes. Eosinophil and cabbage phospholipase D inactivated a partially purified rat platelet-activating factor (PAF) in a time- and dose-dependent reaction. The cleavage of this PAF activity was attributed to the inherent phospholipase D activity of the eosinophil enzyme since the two activities chromatographed together at each purification step, and there was apparent reciprocal inhibition of choline-generating activity by PAF and of PAF-inactivating activity by phosphatidyl choline. Thus, possible regulatory functions of the eosinophil in immediate hypersensitivity reactions include inactivation of a PAF by phospholipase D as well as degradation of slow-reacting substance of anaphylaxis by arylsulfatase B.

Blood Coagulation Factors↗
PubMed2026

IL-13 and calpain-14 suppress the expression of SPINK7 by regulating OVOL1 in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a type 2 allergic disease characterized by esophageal inflammation and epithelial cell dysfunction. The acquired loss of the anti-serine protease of kazal type 7 (anti-SPINK7) in the squamous epithelium of the esophagus has a causal role in EoE pathogenesis. However, there is a limited understanding of the factors that regulate its expression and responsiveness to inflammatory stimuli. Herein, we have identified the transcription factor, ovo like transcriptional repressor 1 (OVOL1), as an esophageal selective gene product that regulates SPINK7 promoter activity. Overexpression of OVOL1 increased SPINK7 expression, whereas its depletion decreased SPINK7 expression, impaired epithelial barrier, and increased production of the proatopy cytokine thymic stromal lymphopoietin (TSLP). Stimulation with IL-13 abrogated the nuclear translocation of OVOL1 and promoted enhanced degradation of OVOL1 protein. This effect of IL-13 was dependent on the esophageal specific cysteine protease calpain-14 at least in part. Analysis of human esophageal biopsies demonstrated that the expression of esophageal OVOL1 correlated with SPINK7 transcript expression and was lost as a function of EoE disease activity. In summary, our study identifies key regulatory mechanisms in EoE pathogenesis, demonstrating that OVOL1 promotes SPINK7 transcription, whereas IL-13 suppresses this pathway in EoE.

Humans↗
PubMed2026

The Potential Link Between Eosinophilic Esophagitis and Food Allergy: Inflammatory Pathogenesis and Management.

Eosinophilic esophagitis (EoE) has transitioned from an isolated gastrointestinal disorder to a recognized type 2 immune-mediated allergic disease, most likely representing a late manifestation of the atopic march. This comprehensive review examines the complex inflammatory pathogenesis linking EoE and food allergy, and critically discusses the mechanisms of disease induction, dietary treatments, and emerging clinical challenges. While genome-wide association studies identify shared susceptibility loci with classic atopy, EoE exhibits distinct tissue-specific pathways, particularly dominated by the local interleukin (IL)-13 axis and highly esophagus-selective proteases like Calpain-14. This unique immunological interplay is clinically epitomized by food oral immunotherapy (OIT)-induced EoE. During OIT, systemic immune reprogramming successfully drives immune tolerance-marked by a robust increase in plasma food-specific IgG4-but fails at the local level, due to the persistence of pathogenic Th2 cells and aberrant mucosal IgG4 immune complex deposition within the esophageal lamina propria. Regarding therapeutic management, conventional skin and serum allergy testing remain highly inaccurate in identifying dietary triggers, rendering test-guided diets ineffective. Conversely, empiric elimination diets achieve robust histological remission, ranging from standardized six-food restrictions to pragmatic single-food approaches targeting cow's milk. Furthermore, novel insights into industrial milk processing (such as UHT sterilization and homogenization) and specific beta-casein genetic variants (A1 vs A2) highlight how altered protein structures generate neoantigens that accelerate esophageal immunogenicity. In conclusion, decoding the divergent immunological mechanisms operating in the refractory esophagus is essential to move beyond trial-and-error dietary interventions towards non-invasive monitoring tools, precision medicine, and optimized biological therapies in EoE management.

Calpain14↗
PubMed2025

Development and Validation an Integrated Deep Learning Model to Assist Eosinophilic Chronic Rhinosinusitis Diagnosis: A Multicenter Study.

BACKGROUND: The assessment of eosinophilic chronic rhinosinusitis (eCRS) lacks accurate non-invasive preoperative prediction methods, relying primarily on invasive histopathological sections. This study aims to use computed tomography (CT) images and clinical parameters to develop an integrated deep learning model for the preoperative identification of eCRS and further explore the biological basis of its predictions. METHODS: A total of 1098 patients with sinus CT images were included from two hospitals and were divided into training, internal, and external test sets. The region of interest of sinus lesions was manually outlined by an experienced radiologist. We utilized three deep learning models (3D-ResNet, 3D-Xception, and HR-Net) to extract features from CT images and calculate deep learning scores. The clinical signature and deep learning score were inputted into a support vector machine for classification. The receiver operating characteristic curve, sensitivity, specificity, and accuracy were used to evaluate the integrated deep learning model. Additionally, proteomic analysis was performed on 34 patients to explore the biological basis of the model's predictions. RESULTS: The area under the curve of the integrated deep learning model to predict eCRS was 0.851 (95% confidence interval [CI]: 0.77-0.93) and 0.821 (95% CI: 0.78-0.86) in the internal and external test sets. Proteomic analysis revealed that in patients predicted to be eCRS, 594 genes were dysregulated, and some of them were associated with pathways and biological processes such as chemokine signaling pathway. CONCLUSIONS: The proposed integrated deep learning model could effectively predict eCRS patients. This study provided a non-invasive way of identifying eCRS to facilitate personalized therapy, which will pave the way toward precision medicine for CRS.

Humans↗
PubMed1976

Central regulation of blood eosinophilia by the beta-adrenergic system in rats.

The effect of isoprenaline and three different beta-adrenergic blocking agents on blood eosinophilia was evaluated in the rat. Eosinopenic effect of isoprenaline was antagonized by intraperitoneal pretreatment with propranolol and by high but not low doses of practolol. Sotalol, a beta-blocker which in contrast to propranolol does not penetrate the blood-brain barrier, did not affect the eosinophil count when injected intraperitoneally, but produced a marked increase in number of circulating eosinophils following intracerebroventricular injection. Intraperitoneal administration of isoprenaline and propranolol as well as intracerebroventricular injection of sotalol did not affect eosinophil count in adrenalectomized or hypophysectomized rats. These results suggest that beta-adrenergic agents regulate the number of circulating eosinophils through a central mechanism and that presence of both hypophysis and adrenal glands is required for this action.

Adrenalectomy↗
PubMed2026

Airway microbiome diversity, intramucosal bacteria, and spatial immunity in asthmatic adults and controls.

RATIONALE: Asthma is characterized by disruption of the thoracic airway mucosae and loss of microbial diversity. Spatial profiling of the mucosal transcriptome may systematically discover mechanisms for microbial influences on immunity. OBJECTIVES: We investigated relationships between clinical measures, microbial communities, and the host mucosal transcriptome within different strata of bronchial biopsies in subjects with and without asthma. METHODS: We performed bronchoscopy in 65 asthmatic adults and 44 healthy controls, quantifying bacterial operational taxonomic units (OTUs) in bronchial brushings by 16S ribosomal RNA (rRNA) gene amplicon sequences. Biopsy histologic features were scored blind to diagnosis. Following 16S rRNA in situ hybridization of 44 biopsies, bacterial foci were scored in epithelium, basement membrane, and stroma. Global human gene expression was quantified in epithelial and stromal compartments using digital spatial profiling. MEASUREMENTS AND MAIN RESULTS: Clinical asthma was independently predicted by basement membrane abnormalities (BaseMA), endobronchial bacterial diversity, and circulating eosinophil counts, but not by specific OTU abundances. 16S rRNA staining revealed bacteria within epithelium and mucosa of all biopsies. Intramucosal bacteria counts correlated negatively with spatially organized coexpression networks encoding antigen-specific immunity, neutrophil functions, and matrix activation, whereas BaseMA correlated positively with the adaptive immunity module. Eosinophil counts correlated with epithelial bacterial counts and senescence pathways. Clinical asthma was accompanied by upregulation of a regulatory T-cell network. CONCLUSIONS: Asthma and its related phenotypes are accompanied by complex mucosal events that extend beyond eosinophilic pathways. Components of diverse airway microbiota may modify immunity by beneficial interactions within the mucosa.

Humans↗
PubMed2026

Prophylactic Inhaled Pattern Recognition Receptor Agonists Reprogram Lung Epithelial Response and Prevent Type 2 Allergic Inflammation.

Prophylactic inhalation of the synergistic agents ODN M362 and Pam2CSK4 ("Pam2ODN") protects mice against allergic lung disease, including allergic inflammation caused by house dust mite (HDM). By preventing sensitization, Pam2ODN reduces HDM-induced eosinophilic and lymphocytic inflammation. How Pam2ODN affects interactions among lung epithelial cells, dendritic cells, and T cells to prevent eosinophilic lung inflammation remains unclear. In the present study, we show that a single inhaled dose of Pam2ODN before HDM sensitization reduces airway Th2 polarization without affecting Th1 or Treg responses. Furthermore, Pam2ODN pretreatment inhibits the recruitment of lung monocyte-derived dendritic cells (moDCs) and conventional Type 2 dendritic cells (DC2s), while preventing the HDM-induced decrease in conventional Type 1 dendritic cells (DC1s). Bulk RNA-seq of the whole lung reveals that Pam2ODN pretreatment restricts the expression of proinflammatory transcripts induced by HDM sensitization. This tolerogenic effect is also reflected at the single-cell level in lung epithelial cells, where proinflammatory transcripts, pathways, and chromatin accessibility are inhibited. These results indicate that Pam2ODN reprograms lung epithelial cells to attenuate allergen-induced Th2-promoting cytokines and DCs while maintaining the population of protective DC1s. These findings suggest a strategy to mitigate chronic allergic lung diseases.

Animals↗
PubMed2026

The Staphylococcus aureus serine protease-like protein B is a potent allergen in a murine asthma model.

BACKGROUND: Asthma is associated with Staphylococcus aureus colonization. Two hypotheses were proposed to explain this phenomenon: (1) the allergic environment in asthma favors S. aureus colonization and (2) S. aureus colonization creates a pro-allergic environment. Since several S. aureus virulence factors, such as the serine protease-like protein (Spl) B, elicit a type 2 biased immune response, we asked whether the pathogen itself can cause asthma. OBJECTIVE: Test the ability of recombinant SplB of S. aureus to sensitize mice and induce allergic airway inflammation (AAI). METHODS: Mice were treated with repeated intratracheal inoculations of either catalytically active SplB or an inactive mutant. AAI was assessed by evaluating airway hypersensitivity, immune cell infiltration, cytokines, mucus production, fibrosis, and specific serum IgE. We compared the outcome between wild-type and gene-deficient C57BL/6J mice, including recombination-activating gene knockout mice (Rag2-/-), interleukin-33 knockout mice (Il33-/-), and protease-activated receptor 2 knockout mice (F2rl1-/-). RESULTS: Intratracheal exposure to SplB sensitized the mice and caused eosinophilic airway inflammation and hyperresponsiveness. The development of asthma required both the proteolytic activity of SplB and a functional adaptive immune system. The soluble protease sensor IL-33 was necessary for eosinophil tissue invasion, whereas the membrane-bound protease sensor PAR2 was not. CONCLUSION: The serine protease SplB of S. aureus is a potent allergen. Based on this finding we propose a third mechanism to explain the relationship between S. aureus colonization and asthma: S. aureus can release allergens, such as SplB, that sensitize individuals and lead to the development of asthma.

Allergy↗
PubMed2025

Ossifying Spindled and Epithelioid Tumor: A Novel Soft Tissue Tumor.

This investigation describes the clinicoradiologic, pathologic, and molecular features of a unique soft tissue tumor characterized by a peripheral shell of bone and composed of bland myoid spindle and epithelioid cells that are keratin-positive. Our study cohort consists of 6 men and 6 women, with a mean age of 32 years. The tumors arose in the extremities (n = 9) and proximal limb girdle (n = 3) and were equally distributed between deep and superficial soft tissues. Patients reported dull painless masses of several months to >10 years duration (mean: 2.9 years). Imaging demonstrated a complete or partial peripheral shell of bone that could extend centrally, and the tumor's mean size was 5.7 cm. Histologically, the tumors were composed of uniform, eosinophilic myoid spindled cells growing in sheets and intersecting fascicles, surrounded by mature lamellar and/or woven bone. Also present was an admixed component of intermediate-sized epithelioid cells with eosinophilic cytoplasm. Mitotic activity was consistently low. Immunohistochemistry showed strong multifocal staining for keratins, and 50% (5/10) showed focal staining for S100; however, all were negative for SMA, desmin, SOX10, ERG, and CD34. Genetic analysis by multiple targeted RNA sequencing panels was negative (n = 10); however, whole transcriptome sequencing (n = 8) revealed a recurrent and novel in-frame SRSF7::NFATC3 fusion in 4 tumors. Dual fluorescence in situ hybridization probes for SRSF7::NFATC3 successfully confirmed this fusion and identified a fifth case, which had not undergone whole transcriptome sequencing but was negative by a targeted RNA fusion panel. Methylation profiling (n = 8) demonstrated a shared epigenetic profile distinct from other entities. Clinical follow-up (n = 11) showed no evidence of recurrence after primary excision with a mean of 41.6 months. In summary, we describe a novel soft tissue tumor designated "ossifying spindled and epithelioid tumor" as a descriptive histologic term that also emphasizes its close radiologic mimic, ossifying fibromyxoid tumor. All cases have behaved in a benign fashion without recurrence following simple excision. Awareness of this entity is important, so that it can be distinguished from other neoplasms that have more aggressive biological potential.

Humans↗
PubMed2026

Hyper-IgE syndromes in pediatrics: clinical spectrum, differential diagnosis, and management.

Hyper-IgE syndromes (HIES) are rare inborn errors of immunity (≈1 per million) caused by pathogenic variants in STAT3, DOCK8 or IL6ST. They present with very high serum immunoglobulin E (IgE), recurrent bacterial or fungal infections, eczema and characteristic organ involvement. The autosomal dominant STAT3-deficient form features early-onset eczema, “cold” abscesses, recurrent pneumonias with pneumatoceles and skeletal or dental anomalies. Autosomal recessive forms such as DOCK8 or PGM3 deficiency show a more severe phenotype with viral skin infections, allergy, asthma and increased malignancy risk. HIES should be suspected in children with IgE >2000 IU/mL plus recurrent sinopulmonary or skin infections, severe eczema, atypical viral infections or a National Institutes of Health Hyper-IgE Syndrome (NIH HIES) score >40. Differentiation from severe atopic dermatitis, asthma, eosinophilic disorders and parasitic infections is essential. Evaluation includes eosinophils, lymphocyte subsets, T-helper 17 (Th17) cell analysis and targeted genetic testing. Management involves antimicrobial prophylaxis, treatment of complications, dermatologic care and genotype-based hematopoietic stem cell transplantation (HSCT), which is curative in DOCK8 but less effective in STAT3 deficiency. Early genomic confirmation enables timely recognition, identification of red flags, and genotype-specific therapy to improve long-term outcomes.

Humans↗
PubMed2026

Genetically predicted associations between blood cell perturbation responses and bronchiectasis through immune mediation: A Mendelian Randomization study.

BACKGROUND: Bronchiectasis is a chronic airway disease characterized by persistent inflammation and structural damage, with substantial clinical and etiologic heterogeneity. Although previous studies have identified associations between blood cells and bronchiectasis, the causal relationships remain unclear. Moreover, the mechanisms underlying blood cell perturbation responses and their potential mediation by immune cells in disease progression are largely unexplored. METHODS: Two-sample Mendelian randomization (MR) analysis was used to explore genetically predicted associations among immune cell traits, blood cell perturbation response phenotypes, and bronchiectasis, based on genome-wide association study summary data. Mediation MR analysis was further applied to assess whether immune cells mediate these associations. Multiple sensitivity analyses, including tests for heterogeneity and horizontal pleiotropy, were performed to evaluate the validity and robustness. RESULTS: Five blood cell perturbation response phenotypes and twenty-nine immune cell traits showed significant genetically predicted associations with bronchiectasis. Mediation analysis showed that natural killer (NK) cell absolute count partially mediated the causal effect between the eosinophil perturbation response and bronchiectasis, with a mediation proportion of 9.626%. CD38 on transitional B cells mediated the causal effect between the monocyte perturbation response and bronchiectasis, with a mediation proportion of 10.580%. Additionally, CD45 on NK cells played a mediating role in the association between the white blood cell perturbation response and bronchiectasis, with a mediation proportion of 10.651%. CONCLUSION: This study systematically explores genetically predicted associations between blood cell perturbation responses and bronchiectasis and highlights potential immune-mediated pathways. These exploratory findings provide novel genetic insights into the pathogenesis of bronchiectasis and identify potential therapeutic targets for future strategies.

Humans↗
PubMed2026

Deep learning and statistical methods identify novel asthma risk variants in Europeans.

BACKGROUND: Asthma is a common heritable respiratory disorder with a complex genetic basis. Although large-scale genome-wide association studies have identified many risk loci, the full spectrum of its polygenic architecture remains to be defined. OBJECTIVE: We refined the genetic landscape of asthma in individuals of European ancestry and improve polygenic risk prediction through statistical and deep learning-based methods. METHODS: We conducted the largest genome-wide association study meta-analysis of asthma in individuals of European ancestry, combining data from the Global Biobank Meta-analysis Initiative (121,940 cases, 1,254,131 controls) and the Million Veteran Program (36,823 cases, 398,278 controls). To enhance discovery, we applied pleiotropy-informed multitrait analysis and conditional false discovery rate approaches, each incorporating eosinophil counts as a secondary trait. In parallel, we used a Transformer-based deep learning framework to further prioritize variants and improve polygenic risk prediction. RESULTS: The meta-analysis identified 69 independent genome-wide significant loci (P&#x2009;<&#x2009;5 &#xd7; 10-8) not previously reported in asthma. Multitrait analysis of genome-wide association studies, conditional false discovery rate, and deep learning approaches uncovered additional candidate loci. Functional annotation and expression quantitative trait locus mapping implicated novel genes in immune regulation, airway remodeling, and metabolic processes. Polygenic risk score models derived from deep learning-prioritized variants outperformed those based on conventional genome-wide association study and standard statistical approaches. CONCLUSIONS: Our study yields a comprehensive map of asthma-associated loci in European ancestry populations, improves genetic risk prediction, and informs future mechanistic studies.

Humans↗
PubMed2025

Intratumoral fungus Neurospora crassa is associated with worsened prognosis in ovarian cancer via modulation of extracellular matrix.

Landmark studies on intratumoral fungi (ITF) have raised concerns due to irreproducible results and data-analysis errors. We aimed to determine whether ITF exist in ovarian cancer (OvCa) and, if so, whether they play a role in disease biology. Formalin-fixed, paraffin-embedded OvCa samples and multiple controls underwent operational decontamination, qPCR, internal transcribed spacer sequencing, and post-hoc data decontamination. We also leveraged updated fungal reads from The Cancer Genome Atlas generated by the TCMbio group, which addressed human-read contamination and artificial inflation, to validate findings and assess prognostic associations. A murine syngeneic model established using mouse ovarian cancer cell line (OVHM) with intratumoral Neurospora crassa injection was established. Transcriptomic and metabolomic analyses were performed to explore mechanisms. Tumor-containing blocks harbored significantly higher fungal loads than environmental controls but had loads comparable to paraffin controls. Applying a two-pass decontamination filter reduced raw sequence features from 9289 amplicon sequence variants (ASVs) to 659 ASVs. We focused on high-abundance features present in human tissues but absent from xenografts and paraffin controls and identified one candidate, N. crassa, associated with unfavorable prognosis in OvCa. Integrating human and murine data, we found Neurospora correlated with eosinophils, whereas N. crassa itself was not immune-related. Neurospora crassa promoted OvCa progression with downregulation of integrin-linked kinase and decreased extracellular matrix-receptor interaction. Most ITF signals are likely contaminants. We identified N. crassa as associated with unfavorable prognosis in OvCa, potentially via modulation of the extracellular matrix.

Neurospora crassa↗
PubMed2024

Revealing differential expression patterns of piRNA in FACS blood cells of SARS-CoV-2 infected patients.

Non-coding RNA expression has shown to have cell type-specificity. The regulatory characteristics of these molecules are impacted by changes in their expression levels. We performed next-generation sequencing and examined small RNA-seq data obtained from 6 different types of blood cells separated by fluorescence-activated cell sorting of severe COVID-19 patients and healthy control donors. In addition to examining the behavior of piRNA in the blood cells of severe SARS-CoV-2 infected patients, our aim was to present a distinct piRNA differential expression portrait for each separate cell type. We observed that depending on the type of cell, different sorted control cells (erythrocytes, monocytes, lymphocytes, eosinophils, basophils, and neutrophils) have altering piRNA expression patterns. After analyzing the expression of piRNAs in each set of sorted cells from patients with severe COVID-19, we observed 3 significantly elevated piRNAs - piR-33,123, piR-34,765, piR-43,768 and 9 downregulated piRNAs in erythrocytes. In lymphocytes, all 19 piRNAs were upregulated. Monocytes were presented with a larger amount of statistically significant piRNA, 5 upregulated (piR-49039 piR-31623, piR-37213, piR-44721, piR-44720) and 35 downregulated. It has been previously shown that piR-31,623 has been associated with respiratory syncytial virus infection, and taking in account the major role of piRNA in transposon silencing, we presume that the differential expression patterns which we observed could be a signal of indirect antiviral activity or a specific antiviral cell state. Additionally, in lymphocytes, all 19 piRNAs were upregulated.

Humans↗