Frontiers in Immunology最新文献

{"title":"Effects of neutrophil granule proteins on sepsis-associated lymphopenia and their relationship with CD4⁺ T-cell pyroptosis.","authors":"Jia-Yu Mao, Ya-Wen Xie, Xian-Li Lei, Jia-Hui Zhang, Wei Cheng, Na Cui","doi":"10.3389/fimmu.2025.1507800","DOIUrl":"10.3389/fimmu.2025.1507800","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil acts as a double-edged sword in the immune system. We hypothesized that an elevated neutrophil granule protein level is associated with sepsis-associated lymphopenia (SAL).</p><p><strong>Methods: </strong>We enrolled 61 patients with sepsis admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital between May 2022 and October 2023 in this study. Clinical and immunological parameters were recorded. Levels of neutrophil granule proteins, including myeloperoxidase (MPO) and neutrophil elastase (NE), and pyroptosis factors were examined.</p><p><strong>Results: </strong>Levels of neutrophil granule proteins (MPO, 82.9 vs. 175.3, <i>p</i> < 0 <.0001; NE, 56.3 vs. 144.2, <i>p</i> < 0.0001) were significantly higher in patients with sepsis with lymphopenia. Neutrophil granule protein levels were independently associated with SAL risk (MPO: OR = 1.0841, 95% CI, 1.0020-1.1730; NE: OR = 1.0540, 95% CI, 1.0040-1.1065). The area under the curve of MPO levels predicting SAL occurrence was 0.939 (95% CI, 0.846-0.984), and that of NE was 0.950 (95% CI, 0.862-0.989). Furthermore, neutrophil granule proteins were significantly correlated with CD4⁺ T cell and its pyroptosis [MPO and CD4⁺ T cells (<i>r</i> = -0.4039, <i>p</i> < 0.0001), CD4⁺NLRP3 (<i>r</i> = 0.4868, <i>p</i> < 0.0001), NE and CD4⁺ T cells (<i>r</i> = -0.5140, <i>p</i> < 0.0001), and CD4⁺NLRP3 (<i>r</i> = 0.6513, <i>p</i> < 0.0001)].</p><p><strong>Conclusion: </strong>Increased levels of neutrophil granule proteins were significantly associated with SAL incidence, and a significant relationship between neutrophil granule proteins and the pyroptosis pathway of CD4⁺ T cells was revealed.</p><p><strong>Clinical trial registration: </strong>chictr.org.cn identifier ChiCTR-ROC-17010750.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1507800"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embryonic heat conditioning induces paternal heredity of immunological cross- tolerance: coordinative role of CpG DNA methylation and miR-200a regulation.","authors":"Padma Malini Ravi, Tatiana Kisliouk, Shelly Druyan, Amit Haron, Mark A Cline, Elizabeth R Gilbert, Noam Meiri","doi":"10.3389/fimmu.2025.1487135","DOIUrl":"10.3389/fimmu.2025.1487135","url":null,"abstract":"<p><strong>Background: </strong>Enhancing an organism's survival hinges on the development of balanced and adaptable stress response systems. While the initial stress-response set-points in the hypothalamus may be genetically determined, they are further influenced by epigenetic factors during embryonic development. A debate persists regarding the heritability of such behavioral traits. The chick <i>in ovo</i> heat conditioning model offers a unique insight into this fundamental question, where manipulation during embryonic development can induce heat resilience and even cross-tolerance to promote immunological resilience. In this study, we conducted an analysis of thermal manipulation during embryogenesis to demonstrate paternal heredity and investigate its transmission through sperm DNA methylation in coordination with miR-200a action.</p><p><strong>Result: </strong>First-generation embryos underwent <i>in ovo</i> heat conditioning (EHC), creating a cohort of embryonic EHC and control chicks. These chicks were then subjected to an intracranial lipopolysaccharide (LPS) challenge. Conditioning rendered the chicks immune resilient, as evidenced by their fibril effect. Male offspring were raised to maturity, and their sperm was analyzed for methylome patterns, revealing significant differences between treatments, particularly in immune and development related genes. Additionally, sperm from EHC males was used for artificial insemination of naïve Cobb hens, resulting in untreated offspring that displayed immune resilience upon LPS challenge, indicating transgenerational effects. Overlap analysis of sperm methylome and differentially methylated sites (DMS) of offspring hypothalamus revealed inheritance of altered methylation associated with specific genes. Several of these genes are potential effectors of miR-200a, whose expression profile in the hypothalamus during LPS challenge was conserved across both generations. To evaluate the role of miR-200a in cross-tolerance acquisition, miR-200a was intracranially injected, and RNA-seq analysis of the hypothalamus revealed genes involved in the regulation of developmental and metabolic processes, stress, and immune response.</p><p><strong>Conclusion: </strong>This study demonstrates paternal trait heredity by revealing that EHC induces cross-tolerance with the immunological system, rendering chicks resilient to LPS that transgenerationally transmit this to untreated offspring. Additionally, analysis of sperm methylation patterns in EHC mature chicks led to identification of genes associated with neuronal development and immune response, indicating potential neural network reorganization. Finally, miR-200a emerges as a regulator potentially involved in mediating the cross-tolerance effect.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1487135"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manipulating the cGAS-STING Axis: advancing innovative strategies for osteosarcoma therapeutics.","authors":"BingBing Li, Cheng Zhang, XiaoJuan Xu, QiQin Shen, ShuNan Luo, JunFeng Hu","doi":"10.3389/fimmu.2025.1539396","DOIUrl":"10.3389/fimmu.2025.1539396","url":null,"abstract":"<p><p>This paper explored the novel approach of targeting the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) pathway for the treatment of osteosarcoma (OS). Osteosarcoma is a common malignancy in adolescents. Most patients die from lung metastasis. It reviewed the epidemiology and pathological characteristics of OS, highlighting its highly malignant nature and tendency for pulmonary metastasis, underscoring the importance of identifying new therapeutic targets. The cGAS-STING pathway was closely associated with the malignant biological behaviors of OS cells, suggesting that targeting this pathway could be a promising therapeutic strategy. Currently, research on the role of the cGAS-STING pathway in OS treatment has been limited, and the underlying mechanisms remain unclear. Therefore, further investigation into the mechanisms of the cGAS-STING pathway in OS and the exploration of therapeutic strategies based on this pathway are of great significance for developing more effective treatments for OS. This paper offered a fresh perspective on the treatment of OS, providing hope for new therapeutic options for OS patients by targeting the cGAS-STING pathway.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1539396"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Nrf2/KEAP1 signaling pathway using bioactive compounds to combat mastitis.","authors":"Muhammad Zahoor Khan, Liangliang Li, Yandong Zhan, Huang Binjiang, Xiaotong Liu, Xiyan Kou, Adnan Khan, Abdul Qadeer, Qudrat Ullah, Khalid J Alzahrani, Tongtong Wang, Changfa Wang, Muhammad Zahoor","doi":"10.3389/fimmu.2025.1425901","DOIUrl":"10.3389/fimmu.2025.1425901","url":null,"abstract":"<p><p>Mastitis is a common inflammation of mammary glands that has a significantly impact on dairy production and animal health, causing considerable economic burdens worldwide. Elevated reactive oxygen species (ROS) followed by oxidative stress, apoptosis, inflammatory changes and suppressed immunity are considered the key biomarkers observed during mastitis. The Nrf2/KEAP1 signaling pathway plays a critical role in regulating antioxidant responses and cellular defense mechanisms. When activated by bioactive compound treatment, Nrf2 translocates to the nucleus and induces the expression of its target genes to exert antioxidant responses. This reduces pathogen-induced oxidative stress and inflammation by inhibiting NF-kB signaling in the mammary glands, one of the prominent pro-inflammatory signaling pathway. Here, we summarize recent studies to highlight the therapeutic potential of Nrf2/KEAP1 pathway in the prevention and treatment of mastitis. Collectively this review article aims to explore the potential of bioactive compounds in mitigating mastitis by targeting the Nrf2/KEAP1 signaling pathway.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1425901"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of inflammatory biomarkers in detecting and managing latent tuberculosis infection.","authors":"Harinisri Gunasekaran, Uma Devi Ranganathan, Ramalingam Bethunaickan","doi":"10.3389/fimmu.2025.1538127","DOIUrl":"10.3389/fimmu.2025.1538127","url":null,"abstract":"<p><p>Infection with <i>Mycobacterium tuberculosis</i> (Mtb) triggers an autoimmune-like response in the host leading to further complications. One of the major concerns in eliminating Tuberculosis (TB) is identifying individuals with Latent Tuberculosis Infection (LTBI) who serve as major reservoirs of Mtb making them the important target group for TB eradication. Since no gold standard tests are available for detecting LTBI, the global burden of LTBI cannot be precisely determined. Since LTBI poses several challenges to worldwide healthcare, managing LTBI must be the key priority to achieve a TB-free status. The inflammatory mediators play a major role in determining the outcome of the Mtb infection and also their levels seem to change according to the disease severity. Identification of inflammatory mediators and utilizing them as diagnostic biomarkers for detecting the various stages of TB disease might help identify the reservoirs of Mtb infection even before they become symptomatic so that preventative treatment can be started early. In summary, this review primarily focuses on exploring different inflammatory markers along the course of the Mtb infection. Identifying LTBI-specific biomarkers helps to identify individuals who are at higher risk of developing TB and preparing them to adhere to preventive therapy thus minimizing the global burden of TB.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1538127"},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current status of cytokine-induced killer cells and combination regimens in breast cancer.","authors":"Yuancong Jiang, Jie Qiu, Nanwei Ye, Yingchun Xu","doi":"10.3389/fimmu.2025.1476644","DOIUrl":"10.3389/fimmu.2025.1476644","url":null,"abstract":"<p><p>Breast cancer remains a significant health challenge worldwide, with substantial efforts aimed at understanding its pathogenesis, biological characteristics, and clinical triggers. Recently, immunotherapy such as the cytokine-induced killer cells combined with other drug therapies has offered new hope for patients with advanced breast cancer. However, the specific pathogenesis of combination regimens involving cytokine-induced killer cells remains elusive. Besides, the combination of immunotherapy with cytokine-induced killer cells might represent a novel breakthrough. This review outlines the current status of cytokine-induced killer cell therapies and their combination strategies, especially the combination of chemotherapy with molecularly targeted treatments, for the management of breast cancer.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1476644"},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of first-line PD-1/PD-L1 inhibitor in combination with CTLA-4 inhibitor in the treatment of patients with advanced non-small cell lung cancer: a systemic review and meta-analysis.","authors":"Huimin Zhao, Shanshan Huang, Jianyu Wu, Yanlan Lu, Yue Zou, Haijian Zeng, Chunlan Li, Jin Wang, Xiaochen Zhang, Siliang Duan, Weiming Liang","doi":"10.3389/fimmu.2025.1515027","DOIUrl":"10.3389/fimmu.2025.1515027","url":null,"abstract":"<p><strong>Introduction: </strong>The combination of PD-1/PD-L1 inhibitor with CTLA-4 inhibitor for advanced non-small cell lung cancer(NSCLC) is presently a significant area of research, however its clinical application remains contentious. This meta-analysis aimed to assess the efficacy and safety of first-line PD-1/PD-L1 inhibitor in combination with CTLA-4 inhibitor (CP) in the treatment of patients with advanced NSCLC.</p><p><strong>Methods: </strong>A systemic search was conducted in four databases (PubMed, Cochrane library, Embase, and Web of Science) from their establishment until January 17, 2024, for randomized controlled trials that investigated the use of the first-line PD-1/PD-L1 inhibitor plus CTLA-4 inhibitor in patients with advanced NSCLC. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were subjected to meta-analyses.</p><p><strong>Results: </strong>Totally 7 eligible randomized controlled trials including 4682 people were included. Two comparative analyses were performed: CP versus chemotherapy, CP versus PD-1/PD-L1 inhibitor (P). Compared with the chemotherapy group, CP improved OS (HR: 0.84, 95% CI: 0.75-0.94, p<0.05) but not PFS (HR: 0.94, 95%CI: 0.73-1.20, p = 0.63) or ORR (OR: 1.16, 95% CI: 0.79-1.71, p = 0.45). In terms of toxicity, CP had slightly fewer any AEs compared to chemotherapy (RR: 0.94, 95% CI: 0.91-0.97; p<0.05). Compared to the P group, there was no significant difference in OS (MD: -0,25, 95% CI: -2.47-1.98, p = 0.83), PFS (MD: -0.91, 95% CI: -3.19-1.36, p = 0.43), and ORR (OR:1.05, 95% CI. 0.80-1.36, p = 0.73). Subgroup analysis revealed that CP provided superior OS compared with P in patients with PD-L1 expression < 1%.</p><p><strong>Conclusion: </strong>CP was a feasible and safe first-line therapy for patients with advanced NSCLC. Specifically, CP may function as a therapeutic alternative for individuals with low or negative PD-L1 expression, resulting in enhanced long-term outcomes compared to chemotherapy or P. Further randomized controlled trials with prolonged follow-up periods are necessary to validate these results, particularly focusing on efficacy in patients with differing PD-L1 expression levels, to improve the stratified implementation of immunotherapy.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024621116, identifier CRD42024621116.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1515027"},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: Significant lesion reduction and neural structural changes following ibogaine treatments for multiple sclerosis.","authors":"David Qixiang Chen, José Adalberto Inzunza Domínguez, Juan Manuel Valle Uzeta, Abhiram P Pushparaj, Jonathan E Dickinson","doi":"10.3389/fimmu.2025.1535782","DOIUrl":"10.3389/fimmu.2025.1535782","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a debilitating neurodegenerative disease characterized by demyelination and neuronal loss. Traditional therapies often fail to halt disease progression or reverse neurological deficits. Ibogaine, a psychoactive alkaloid, has been proposed as a potential neuroregenerative agent due to its multifaceted pharmacological profile. We present two case studies of MS patients who underwent a novel ibogaine treatment, highlighting significant neuroimaging changes and clinical improvements. Patient A demonstrated substantial lesion shrinkage and decreased Apparent Diffusion Coefficient (ADC) values, suggesting remyelination and reduced inflammation. Both patients exhibited cortical and subcortical alterations, particularly in regions associated with pain and emotional processing. These findings suggest that ibogaine may promote neuroplasticity and modulate neurocircuitry involved in MS pathology.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1535782"},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful sequential therapy with rituximab and telitacicept in refractory Anti-NMDA receptor encephalitis and MOG-associated demyelination: a case report and literature review.","authors":"Jingliang Zhang, Minzhe Hu, Chunjuan Wang, Shougang Guo","doi":"10.3389/fimmu.2025.1509143","DOIUrl":"10.3389/fimmu.2025.1509143","url":null,"abstract":"<p><p>Clinical management of the rare and complex overlapping syndrome of MOG-antibody disease and anti-NMDAR encephalitis (MNOS), which has an uncertain pathogenesis and a high risk of recurrence, is highly challenging. We describe the case of a 19 years-old female patient, who first complained of headache, fever, and irritability. After that, she experienced frequent seizures and mood disorders. The diagnosis of MNOS was verified through antibody tests and imaging. For the patient, intravenous immunoglobulin and high-dose methylprednisolone were effective as first-line immunotherapy. Long-term immunotherapy with oral prednisone and mycophenolate mofetil was used to prevent relapses. However, over six years, the patient had five relapses when the mycophenolate mofetil dosage was reduced. The patient's condition stabilized after taking rituximab as second-line immunotherapy, with less than 1% of total lymphocytes being CD19+ cells. Eleven months later, the plasmablast ratio increased, and patients experienced new symptoms such as bilateral optic neuritis. After that, the patient got telitacicept injections regularly for 13 months, during which time her symptoms subsided, and there were no adverse effects or relapses. This case suggests that telitacicept may be a viable adjunct or sequential therapy option for the depletion of B cells in MNOS.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1509143"},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary and systemic immune alterations in rats exposed to airborne lunar dust.","authors":"Brian E Crucian, Heather Quiriarte, Chiu-Wing Lam, Mayra Nelman, Audrie A Colorado, Douglass M Diak, John T James","doi":"10.3389/fimmu.2025.1538421","DOIUrl":"10.3389/fimmu.2025.1538421","url":null,"abstract":"<p><strong>Background: </strong>Due to cosmic radiation bombardment and over 4 billion meteorite and micrometeoroid impacts on the airless Moon, the lunar surface is covered by a layer of fine, reactive dust. Very little is known regarding the toxicity of lunar dust on human physiology. This study assessed airborne lunar dust exposure in rats on localized pulmonary and systemic immune parameters.</p><p><strong>Methods: </strong>Rats were exposed to 0 (air only), 20.8 (low), and 60.6 (high) mg/m³ of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week). Rats were then euthanized either 1 day, 7 days, 4 weeks, or 13 weeks after the last exposure. Peripheral blood and lung lavage fluid samples were collected for analysis. Assays included leukocyte distribution by multicolor flow cytometry and electron/fluorescent microscopy to visualize cell-particulate interactions and lavage/plasma cytokine concentration. Mitogen-stimulated cytokine production profiles, as a measure of cellular function, were performed on whole blood samples only.</p><p><strong>Results: </strong>Untreated lavage fluid was comprised primarily of pulmonary macrophages. High-dose lunar dust inhalation (60.6 mg/m³) resulted in an influx of both neutrophils and lymphocytes. Although the percentage of lymphocytes increased, the T-cell CD4:CD8 ratio was unchanged. Cytokine analysis of the lavage fluid showed increased levels of IL-1β and TNFα. These alterations generally persisted through the 13-week sampling. Blood analysis showed few systemic immune alterations from the lunar dust inhalation. By week 4, the peripheral granulocyte percentage was elevated in the treated rats. Plasma cytokine levels were unchanged in all treated rats compared to controls; however, altered mitogen-stimulated cytokine production profiles were observed consisting of increased IL-1β and IL-6 and decreased IL-2. There were minimal adverse immune effects, in both lung or peripheral blood, following low-dose exposure to 20.8 mg/m³ lunar dust.</p><p><strong>Conclusion: </strong>Exposures to high concentrations of lunar dust resulted in persistent lung inflammation and some systemic immune dysregulation that did not subside even 13 weeks after the dust exposure. This information is beneficial in deriving an exposure limit to airborne lunar dust and for spacecraft engineers considering dust mitigation systems in lunar landers or habitats.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1538421"},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}