Journal of Immunotoxicology最新文献

{"title":"In Memorial: Kenneth L. Hastings, DrPH, DABT, FATS.","authors":"Robert V House, Marc J Pallardy","doi":"10.1080/1547691X.2026.2639297","DOIUrl":"https://doi.org/10.1080/1547691X.2026.2639297","url":null,"abstract":"","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"23 1","pages":"2639297"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344461","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":"Evaluation of the immunotoxicity of atrazine and its chloro-metabolites: relevance for human cancer.","authors":"Charles Breckenridge, James W Simpkins, Ralph Cooper","doi":"10.1080/1547691X.2025.2604501","DOIUrl":"https://doi.org/10.1080/1547691X.2025.2604501","url":null,"abstract":"<p><p>This review was undertaken because it is known that high doses of atrazine activate the HPA axis, leading to increased corticosterone secretion, which could result in immunosuppression.  The mammalian immunotoxicity of atrazine was evaluated based on <i>in vitro</i> and <i>in vivo</i> studies and the association between chlorotriazine use and the risk of cancer in humans based on epidemiological studies. <i>In vitro</i> studies reported that μM concentrations of atrazine may adversely affect cytokine production, lymphocytes, and dendritic cell function. However, there were no consistent patterns of effects of the chlorotriazines on the developing or mature immune system in sub-chronic, chronic, and lifetime animal studies. In a detailed immunotoxicity study on atrazine in rats, there were no effects of atrazine treatment on T-cell-dependent, IgM antibody production or natural killer cell activity. Based on the compendium of toxicology data reviewed, it was concluded that atrazine is unlikely to be immunotoxic at any dose to which humans might realistically be exposed. This conclusion was supported by epidemiological studies indicating that there was no consistent association between occupational exposure to atrazine and cancers of the immune system.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"23 1","pages":"2604501"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018614","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":"Evaluating miRNAs as predictive biomarkers for drug-induced autoimmune toxicity in D-penicillamine induced autoimmune diseases animal model.","authors":"Ren Yuke, Qu Zhe, Zhang Di, Yang Yanwei, Huo Guitao, Li Shuangxing, Jiang Hua, Li Lulu, Lin Zhi","doi":"10.1080/1547691X.2026.2622342","DOIUrl":"https://doi.org/10.1080/1547691X.2026.2622342","url":null,"abstract":"<p><p>Drug-induced autoimmune (DIA) toxicity represents a significant challenge in drug safety evaluation, and traditional autoantibody biomarker antinuclear antibodies (ANA) exhibits limitations in DIA assessment, highlighting the urgent need for more reliable biomarkers. This study employed d-penicillamine to induce an autoimmune disease model in Brown Norway (BN) rats and systematically investigated the expression changes of autoimmunity-related microRNAs (miRNAs) in spleen, exploring their potential value as novel biomarkers for predicting DIA toxicity. A total of 30 male BN rats were randomly divided into control group (0 mg/kg), low-dose d-penicillamine group (150 mg/kg), and high-dose group (450 mg/kg), with necropsy performed at days 7 and 14 post-administration. ANA detection, histopathological examination of spleen, surface immune-related proteins CD11a and CD278 on splenic CD3⁺CD4⁺ T-cells, and miRNA expression profiling in spleen tissue were conducted. Receiver operating characteristic (ROC) curves were plotted to evaluate the correlation of ANA and miRNAs with the degree of splenic pathological damage, and the relationships between miRNAs and both ANA and CD11a/CD278 were analyzed. The results demonstrated that 16 miRNAs were significantly up-regulated in spleen tissue, among which 13 miRNAs showed superior predictive performance (AUC = 0.828-0.898) compared to the traditional biomarker ANA (AUC = 0.783), with most of these miRNAs exhibiting correlation with CD11a/CD278 expression. These findings indicate that aberrant miRNA expression in the d-penicillamine-induced autoimmune disease preclinical model in BN rats holds potential for early prediction of DIA toxicity, with some miRNAs demonstrating higher diagnostic value than ANA, thereby providing novel molecular biomarker candidates for early diagnosis of DIA toxicity.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"23 1","pages":"2622342"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729198","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":"Micro- and nanoplastics-mediated immunometabolic reprogramming: a systemic nexus for chronic inflammation and multi-organ disease risk.","authors":"Jingxuan Dai, Kun Yuan, Keming Huang, Yingyan Sun, Xuancheng Zhou, Ying Zhang","doi":"10.1080/1547691X.2026.2665189","DOIUrl":"https://doi.org/10.1080/1547691X.2026.2665189","url":null,"abstract":"<p><p>Micro- and nanoplastics (MNP) are ubiquitous environmental stressors increasingly detected in human tissues and directly linked to clinical cardiovascular events. This review proposes immunometabolic reprogramming as the central nexus through which MNP drive systemic immune dysregulation and chronic inflammation. Upon entering <i>via</i> multiple routes, MNP selectively sequester in immune organs, disrupting mitochondrial quality control <i>via</i> Drp1-mediated fission and activating the cGAS-STING pathway. Furthermore, MNP induce a pseudohypoxic state that stabilizes HIF-1a, driving a glycolytic \"Warburg-like\" shift that promotes pro-inflammatory macrophage polarization. These intracellular perturbations are further amplified by \"lipid corona\" formation and gut microbiota dysbiosis, which depletes anti-inflammatory short-chain fatty acids. Collectively, this systemic immunometabolic remodeling provides a mechanistic framework for understanding MNP-related risks for cardiovascular, metabolic, and neurodegenerative disorders.  This review emphasizes the necessity of integrating immunometabolic parameters into future environmental health risk assessment frameworks.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"23 1","pages":"2665189"},"PeriodicalIF":3.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838865","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":"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":"https://doi.org/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":3.1,"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":"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":"https://doi.org/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":3.1,"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":"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":"https://doi.org/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":3.1,"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}