Journal of Immunotoxicology最新文献

{"title":"Lung microbiota dysbiosis mediates PM_2.5-induced pulmonary inflammation through antibiotic-reversible mechanisms.","authors":"Yongfei Zheng, Lin Zhang, Jiaqi Tian, Ning Li, Qiang Li, Fei Li, Jiahua Meng, Zitong Zhang, Xiang Yun, Shuyin Duan","doi":"10.1080/1547691X.2026.2660647","DOIUrl":"10.1080/1547691X.2026.2660647","url":null,"abstract":"<p><p>Fine particulate matter (PM_2.5) exposure contributes to over 4 million premature deaths annually, yet the mechanistic role of lung microbiota in PM_2.5-induced pulmonary inflammation remains poorly understood. In collaboration of 16S rRNA and single-cell RNA multi-omics analysis and <i>in vivo/in vitro</i> experimental validation with antibiotic intervention strategies, the study here examined PM_2.5-microbiota interactions in murine PM_2.5 exposure models and cellular systems. It was found that PM_2.5 exposure induced lung microbiota dysbiosis characterized by Gram-negative bacterial expansion, particularly <i>Proteobacteria</i> dominance, accompanied by reduced microbial diversity. scRNA analysis revealed coordinated activation of TLR4/MyD88/NLRP3 inflammatory signaling pathways and p53/p21/p16-mediated cell cycle arrest. Moreover, PM_2.5 exposure activated NLRP3 inflammosome-dependent macrophage pyroptosis as evidenced by increased interleukin (IL)-1β, IL-18, caspase-1, and GSDMD expression. <i>In vitro</i> studies demonstrated that the inflammatory changes induced by PM_2.5 exposure were statistically indistinguishable from those of LPS-positive controls, confirming endotoxin-like mechanisms. Critically, antibiotic pretreatment effectively attenuated PM_2.5-induced inflammatory responses, cell cycle arrest, and tissue pathology, which established causality between microbiota disruption and pulmonary dysfunction. In conclusion, this study revealed lung microbiota dysbiosis as a critical mediator of PM_2.5-induced pulmonary inflammation through Gram-negative bacterial expansion and subsequent endotoxin-like activation of inflammatory cascades, thereby providing novel mechanistic insights and potential microbiome-targeted therapeutic strategies for air pollution-associated respiratory diseases.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"23 1","pages":"2660647"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statement of Retraction: Long non-coding RNA PMS2L2 is down-regulated in osteoarthritis and inhibits chondrocyte proliferation by up-regulating miR-34a.","authors":"","doi":"10.1080/1547691X.2026.2712204","DOIUrl":"https://doi.org/10.1080/1547691X.2026.2712204","url":null,"abstract":"","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"23 1","pages":"2712204"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modification of the dextran sodium sulfate model to identify agents that induce or exacerbate inflammatory bowel disease.","authors":"Victor J Johnson, Michael I Luster, Michael Kashon, Erin M Quist, Gary R Burleson, Florence G Burleson, Dori R Germolec","doi":"10.1080/1547691X.2025.2594800","DOIUrl":"10.1080/1547691X.2025.2594800","url":null,"abstract":"<p><p>Exposure to environmental agents has been linked to inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD) in humans. In these studies, we describe a modification of an experimental model used historically in the pharmaceutical industry to help identify therapies for the treatment of IBD to facilitate its use for identification of environmental agents that have the potential to accelerate, exacerbate, and/or impair recovery from IBD. In this model, female C57BL/6 mice were exposed to low levels of dextran sodium sulfate (DSS) for 7 consecutive days in drinking water to allow for a modest level of colon inflammation and pathology as measured by a battery of clinical, pathological, toxicological endpoints (water consumption, body weights, colon length, body temperature, stool consistency, and hematochezia), and cytokine/chemokine production in the serum and colon. Treatment with DSS for 7 d showed a clear dose-response with 1% DSS producing minimal changes in the colon and 3% DSS inducing severe damage with IBD. A concentration of 2% DSS in drinking water for 7 d was selected for investigating disease recovery and exacerbation by an environmental agent as it induced mild colon inflammation that showed nearly complete resolution within 21 d following cessation of DSS exposure. Cytokine and chemokine profiles showed a Type 1 predominant immune response in the colon and serum that is consistent with inflammation observed in human IBD. The model was used to determine the impact of administration of a high salt diet (HSD) on DSS IBD progression, severity, and recovery. While administration of HSD by itself had no effect on indicators of colon damage or inflammation, co-administration of HSD with DSS, produced marked exacerbation and persistence of disease supporting the potential of the model for identifying environmental agents that can affect IBD.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"23 1","pages":"2594800"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12882113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145856977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between patient risk factors, disease severity, and inflammatory markers in community-acquired pneumonia.","authors":"Ruta Nutautiene, Irmantas Aleksa, Ieva Janulaityte, Asta Maciuliene, Kristina Bieksiene, Diana Zaliaduonyte, Astra Vitkauskiene","doi":"10.1080/1547691X.2026.2640339","DOIUrl":"10.1080/1547691X.2026.2640339","url":null,"abstract":"<p><p>Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality, particularly in older adults and patients with chronic co-morbidities. Cytokine patterns and simple hematological indices may improve risk stratification beyond conventional clinical scores. In this prospective single-center study, 41 adults with CAP treated at Kaunas Hospital of Lithuanian University of Health Sciences between November 2024 and March 2025 were enrolled. Clinical data, pneumonia severity index (PSI), complete blood count-derived indices (neutrophil-lymphocyte ratio [NLR], platelet-lymphocyte ratio [PLR], systemic immune-inflammation index [SII]), and serum concentrations of interleukin (IL)-6, IL-8, interferon (IFN)-γ, and G-CSF were obtained on admission (Visit 1) and after 7 days of treatment (Visit 2). Patients were stratified by age (≤65 vs >65 years), co-morbidities, and PSI class. Non-parametric tests and Spearman correlations were applied. The results indicate that patients with co-morbidities and those > 65 years had significantly higher IL-6 levels than younger and non-comorbid patients. IL-6, IFNγ, and G-CSF concentrations were highest at admission and declined by day 7, particularly in PSI Class II patients. Higher PSI classes were associated with increased IL-8, IL-6, and IFNγ. NLR and SII were significantly higher in older patients and in PSI III-IV compared with PSI I-II. IL-6 and G-CSF showed strong positive correlations with NLR and SII, especially in elderly and comorbid patients, whereas PLR displayed weaker and less consistent associations. From these data, it is concluded that in CAP, serum IL-6, IFNγ, and G-CSF reflect age, co-morbidity burden, and disease severity, while NLR and SII closely mirror cytokine-driven systemic inflammation. These readily available indices may serve as cost-effective prognostic markers and, combined with cytokine profiling, could enhance early risk stratification and guide individualized management in CAP.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"23 1","pages":"2640339"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seasonal variation in cytokine profiles in atopic dermatitis patients treated with dupilumab.","authors":"Jarmila Čelakovská, Eva Čermáková, Petra Boudkova, Ctirad Andrýs, Jan Krejsek","doi":"10.1080/1547691X.2026.2680953","DOIUrl":"https://doi.org/10.1080/1547691X.2026.2680953","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is primarily a T_H2-driven pathology, yet seasonal factors may activate additional immune pathways. This study examined seasonal variation in plasma cytokines in adults with AD treated with dupilumab (<i>N</i> = 20), AD patients without systemic therapy (<i>N</i> = 15), and healthy controls (<i>N</i> = 34). Cytokines (interleukin [IL]-17A, thymic stromal lymphopoietin (TSLP), interferon (IFN)γ, tumor necrosis factor (TNFα), IL-2, IL-6, IL-12p70, IL-23, and IL-31) were measured during summer and winter under unstimulated and phorbol 12-myristate 13-acetate (PMA)/ionomycin-stimulated conditions. Dupilumab-treated patients showed significant winter increases in stimulated IFNγ, TNFα, IL-2, IL-6, and TSLP, indicating preserved inducible T_H1/innate and alarmin activity. Untreated AD patients displayed winter elevation of stimulated IL-6 and unstimulated IFNγ, while healthy controls showed broad winter up-regulation of stimulated T_H1/innate cytokines. Higher winter cytokine levels tended to occur in dupilumab-treated patients with scoring atopic dermatitis (SCORAD) > 10 (evaluation of severity AD - scoring of atopic dermatitis). The findings obtained here suggest that seasonal environmental factors modulate immune responses even under biologic therapy, supporting season-aware, individualized AD management.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"23 1","pages":"2680953"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embryonic exposure to ambient concentrations of PFAS impairs the innate immune response in zebrafish and fathead minnow.","authors":"Samantha Lyons, Alder M Yu, Gavin K Dehnert, Tisha C King Heiden","doi":"10.1080/1547691X.2026.2728992","DOIUrl":"https://doi.org/10.1080/1547691X.2026.2728992","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants associated with immunotoxicity; however, their effect on innate immune function in fish at ambient concentrations remains unclear. Perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) are legacy PFAS prevalent in aquatic ecosystems and have been well studied in zebrafish at high concentrations.  The present study evaluated the effects of embryonic exposure (morula through 2 days post hatch) to environmentally relevant concentrations of PFOS or PFHxS (∼0.8-800 ng/L) on the innate immune response of zebrafish (<i>Danio rerio</i>) and fathead minnow (<i>Pimephales promelas</i>). Impacts on the innate immune response were assessed by quantifying neutrophil recruitment and an <i>in vivo</i> respiratory burst. Neutrophil migration was impacted more in fathead minnows, while zebrafish had greater alterations in the respiratory burst. Fathead minnows were more sensitive than zebrafish with respect to the overall response, and PFHxS was slightly more immunotoxic than PFOS. <i>In silico</i> comparison of the peroxisome proliferator-activated receptor (PPARΥ) predicts that the fathead minnow receptor could have a stronger ligand-binding affinity. These findings demonstrate that environmentally- relevant PFHxS or PFOS exposures can suppress innate immune function in a species specific and non-monotonic dose response, potentially increasing susceptibility to pathogen-induced mortality in fish.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"23 1","pages":"2728992"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The beneficial properties of glycomacropeptide in management of atopic dermatitis and extenuating skin aging.","authors":"Lida Majidinia, Ladan Majidinia, Ahmad Kalbasi-Ashtari","doi":"10.1080/1547691X.2026.2619154","DOIUrl":"10.1080/1547691X.2026.2619154","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by impaired skin barrier function, persistent inflammation, and increased vulnerability to environmental irritants. Chronic inflammation in AD can also contribute to premature skin aging by promoting collagen degradation, wrinkle formation, and reduced skin elasticity. Conventional treatments, including topical corticosteroids, may lead to adverse effects with long-term use, underscoring the need for safer, sustainable alternatives. Glycomacropeptide (GMP), a bioactive peptide derived from κ-casein during cheese production, has attracted interest for its anti-inflammatory, antioxidant, and skin barrier-supporting properties. Evidence from <i>in vitro</i>, <i>in vivo</i>, and limited clinical studies suggests that GMP may modulate inflammatory responses, attenuate oxidative stress, support collagen integrity, and promote wound healing. Its amphiphilic nature also enables its use as a natural emulsifier in topical formulations. In addition, the utilization of GMP contributes to sustainable development by valorizing dairy byproducts. This narrative review synthesizes current literature on GMP's dermatological potential, with a focus on its applicability in AD management and skin aging mitigation, while identifying research gaps and directions for future clinical evaluation.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"23 1","pages":"2619154"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction between expression of CD23 on B-lymphocytes and level of specific IgE against molecular components of NPC2 family, lipocalins, uteroglobins, and molecular components of molds and yeast.","authors":"Jarmila Čelakovská, Petra Boudkova, Eva Cermakova, Ctirad Andrys","doi":"10.1080/1547691X.2025.2531794","DOIUrl":"https://doi.org/10.1080/1547691X.2025.2531794","url":null,"abstract":"<p><p>The aim of this study was to assess the relationship between the expression of the CD23 molecule on B-cells and the levels of specific IgE against allergens and molecular components of storage mites (Gly d 2, Lep d 2), dog (Can f 1, Can f 2), cat (Fel d 1), shrimp (Pen m 2), molds (Asp f 6, Mala s 11, Alt a 6, Alt a 1, Mala s 6, Cla h), and German cockroach (Bla g 9) in atopic dermatitis (AD) patients (with and without dupilumab therapy). Here, 46 patients with AD were included (26 without dupilumab treatment, 20 with dupilumab treatment). Serum levels of specific IgE were measured using the component-resolved diagnostic microarray ALEX2 Allergy Xplorer, and the expression of the CD23 molecule on B-cells was evaluated using flow cytometry. For statistical analysis, a Spearman's rank correlation was used. The data indicated there was a higher correlation between CD23 expression on B-cells and specific IgE against molecular components of storage mites Bla g 9 (up to 27%), cat Fel d 1 (22.7%), and allergen extract Cla h (<i>Cladosporium herbarum</i>) up to 38.9% in AD patients treated with dupilumab. These results regarding the higher association suggested a significant role in the non-inflammatory clearance and uptake of these specific IgE antibodies.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2531794"},"PeriodicalIF":3.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunophenotypical characterization of immune checkpoint receptor expression in cynomolgus monkeys and human healthy volunteers in resting and in T-cell stimulatory conditions <i>in vitro</i>.","authors":"Danielle Craig-Meyer, Joseph A Hollenbaugh, Sara Morgado, Karen McGee, Ethan Perkins, Brogan Yarzabek, Philip Lapinski, Amber Rowse, Chris Cooper, Mara Fortunato, Mario Cocco, Karen Cadwallader, James Munday","doi":"10.1080/1547691X.2025.2462106","DOIUrl":"10.1080/1547691X.2025.2462106","url":null,"abstract":"<p><p>Immunotherapeutics targeting immune checkpoint receptors or their ligands (i.e., immune checkpoint inhibitors), have been groundbreaking in the field of oncology, radically changing the approach to treatment and improving the clinical outcomes of an ever-expanding list of solid tumors and hematological malignancies. However, immune checkpoint inhibitors (ICI) are not devoid of side effects, collectively regarded as immune-related adverse events (irAE); they are not easily uncovered in preclinical immunotoxicological investigations and are often due to the very low expression of their targets in immunologically-unchallenged non-clinical species. We have characterized expression of a broad range of immune checkpoint receptors in peripheral blood mononuclear cell (PBMC) subpopulations from cynomolgus monkeys and healthy human volunteers, under resting and T-cell stimulatory conditions by multicolor flow cytometry to inform appropriate species selection for modeling potential irAE in immunotherapeutic preclinical research. Focusing on the response of the main lymphocyte populations to interleukin (IL)-2 alone, or in combination with anti-CD3 and anti-CD28 antibodies, checkpoints with shared similarities and key differences between the two species were identified. The results of this first study provide a database for the expression and response to stimulation for immune checkpoint receptors and can help guide future model selection in the design of preclinical studies involving immunotherapeutics directed against these targets.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2462106"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparable immunogenicity of new modality biotherapeutics delivered subcutaneously or intravenously in non-human primates.","authors":"Victoria Koch, Martin Lechmann, Katharine Bray-French, Matthias Füth, Elisabeth Husar, Niels Janssen, Anneliese Schneider, Kay Stubenrauch, Timothy Hickling, Sven Kronenberg","doi":"10.1080/1547691X.2025.2537408","DOIUrl":"10.1080/1547691X.2025.2537408","url":null,"abstract":"<p><p>Unwanted immunogenicity of therapeutic proteins arises through the combination of many factors, with the route of administration considered a significant contributor. Contrary to historic data on vaccine delivery, analysis of various therapeutic protein products indicates that the subcutaneous route is not a systematic risk. However, individual product assessments may identify factors specific to the circumstance of their use. Preclinical <i>in vivo</i> studies may add additional information to the comparative immunogenicity risk assessment of intravenous versus subcutaneous administrations. Moreover, immunogenicity risk assessment of new biotherapeutic modalities, such as bispecific antibodies and antibody-linked cytokines, may benefit from a full analysis of risk factors, including preclinical <i>in vivo</i> data. The study here provides immunogenicity analysis of an IgG, two CD3 bispecific antibodies, and two Fc-linked immunocytokines administered intravenously and subcutaneously, aiming to highlight similarities and differences between these administration routes. The current results suggest that the development of anti-drug antibodies does not solely depend on the route of administration but is influenced by multiple risk factors, which should be addressed on a case-by-case basis. This paper reflects on the challenges of interpreting the data and propose standards for improving sample and data collection to aid future analysis.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"22 1","pages":"2537408"},"PeriodicalIF":3.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}