Immunobiology最新文献

{"title":"Preclinical models of immune checkpoint inhibitors-related interstitial pneumonia for anti-PD1 tumor immunotherapy","authors":"Tingyue Luo ,&nbsp;Weisheng Chen ,&nbsp;Danhui Huang ,&nbsp;Xiguang Liu ,&nbsp;Junjie Xi ,&nbsp;Zeyu Fu ,&nbsp;Junwei Chen ,&nbsp;Yuhan Du ,&nbsp;Ruijun Cai ,&nbsp;Qi Yu ,&nbsp;Dongyu Liu ,&nbsp;Jiangzhou Du ,&nbsp;Laiyu Liu ,&nbsp;Shaoxi Cai ,&nbsp;Hangming Dong","doi":"10.1016/j.imbio.2025.152884","DOIUrl":"10.1016/j.imbio.2025.152884","url":null,"abstract":"<div><div>Immune-related adverse reactions (irAEs) are common adverse reactions after immune checkpoint inhibitor treatment, impacting the universality and continued use of immunotherapy. Currently, preclinical models to investigate the mechanisms underlying these adverse effects are inadequate. This study aims to develop both in vitro and in vivo models of irAEs to advance basic research on these adverse reactions. For vitro models, we designed two co-culture systems: “Lung epithelial cells-PBMC” conditional co-culture model and “organoid-PBMCs” co-culture model. These involve culturing spheroids, patient-derived organoids and isolating, expanding, and co-culturing peripheral blood mononuclear cells (PBMCs). For vivo model, PD1 humanized mice were used to establish a lung carcinoma in situ model in offspring, with blocked immune checkpoints to induce systemic inflammatory responses. Mice without PD-1 blockade served as the control group. In both organoid and “lung epithelial cell-PBMC” models, compared with the control group, the PBMC+anti-PD1 group exhibited inflammatory injury, demonstrated by the worst activity, increased collagen deposition, elevated mRNA levels of αSMA and Vimentin, higher Fibronectin expression, and higher inflammatory factors (IL6, IL1β, MPO) in the culture supernatant (<em>p</em> &lt; 0.05). In vivo model also showed pulmonary inflammation, with slower weight gain of the affected mice, more obvious pulmonary interstitial thickening(Masson staining and α-SMA immunofluorescence staining), and increased immune cells and IL17A in alveolar lavage fluid and serum. This study successfully developed preclinical models of irAEs using organoid technology, conditioned co-culture and humanized mouse models, effectively reproducing inflammatory injury and offering valuable tools for irAE research.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152884"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454631","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":"Shared pyroptosis pathways and crosstalk genes underpin inflammatory links between periodontitis and atherosclerosis","authors":"Pinxin Zhan,&nbsp;Zhiying Feng,&nbsp;Xinqi Huang,&nbsp;Haoyang Xu,&nbsp;Shijun Xu,&nbsp;Shan Wang","doi":"10.1016/j.imbio.2025.152880","DOIUrl":"10.1016/j.imbio.2025.152880","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to identify crosstalk genes shared between periodontitis (PD) and atherosclerosis (AS) and to investigate their potential connections with pyroptosis-related genes. The goal was to uncover common regulatory mechanisms underlying these two inflammatory conditions.</div></div><div><h3>Methods</h3><div>Gene expression datasets for PD (GSE10334) and AS (GSE43292) were retrieved from public databases. Following batch effect correction and normalization, differential expression analysis was conducted using the limma package in R. Functional enrichment analysis was performed with the clusterProfiler package to identify key pathways, while heatmaps and pathway networks were constructed to visualize the relationships among pyroptosis genes and crosstalk genes. Weighted gene co-expression network analysis (WGCNA) was applied to identify critical modules, and the diagnostic potential of core genes was evaluated via receiver operating characteristic (ROC) analysis. Protein-protein interaction (PPI) networks were also constructed to explore molecular interactions.</div></div><div><h3>Results</h3><div>A total of 28 downregulated and 105 upregulated genes were identified in the PD dataset, while the AS dataset revealed 55 downregulated and 56 upregulated genes. Thirteen crosstalk genes were identified between the two datasets. Enrichment analyses of these crosstalk genes highlighted their involvement in inflammation- and immune-related pathways. The observed association of pyrototic phenotypes with PD and AS indicated significant overexpression of pyroptosis-related genes such as CASP1, NLRP3, and GSDMD, suggesting the participation of pyroptosis in the progression of disease. The WGCNA suggested that pyroptosis genes are closely relevant to immune responses and cell death processes. Data up to October 2023 were used to perform receiver operating characteristics (ROC) curves to confirm the diagnostic value of the enriched core genes, and all of them presented AUC values &gt;0.8, which meant that they were key genes with effective diagnostic power.</div></div><div><h3>Conclusion</h3><div>We report a novel study that identifies differentially expressed genes and pyroptosis-related pathways in PD and AS with shared inflammatory mechanisms. These results underscore the crucial role of pyroptosis in disease progression, suggesting its potential as a focus of diagnostic and therapeutic strategies. These findings provide insights for dissecting the molecular basis of inflammatory diseases.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152880"},"PeriodicalIF":2.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444425","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":"Expression of human superoxide dismutase (SOD) 1 G93A and chlorovirus ATCV-1 SOD increases the response of macrophages to inflammatory stimulants, including ATCV-1 major capsid protein glycans","authors":"Thomas M. Petro ,&nbsp;Ahmed Esmael ,&nbsp;Gary L. Pattee ,&nbsp;Fiyad Al-Sarmi ,&nbsp;Fabrizio Chiodo ,&nbsp;Irina V. Agarkova ,&nbsp;David D. Dunigan ,&nbsp;James L. Van Etten","doi":"10.1016/j.imbio.2025.152881","DOIUrl":"10.1016/j.imbio.2025.152881","url":null,"abstract":"<div><div>One cause of familial Amyotrophic Lateral Sclerosis (ALS) is a mutation in Super Oxide Dismutase 1 (SOD1) whereby amino acid 93 is alanine instead of glycine (SOD1-G93A). Transgenic mice expressing human SOD1-G93A pathogenic variant develop motor neuron disease (MND), similar to ALS. Humans with ALS and SOD1-G93A mice have elevated production of inflammatory cytokines, such as IL-6, which may promote MND. We previously showed that infection with the Chlorovirus <em>Acanthocystis turfacea</em> chlorella virus 1 (ATCV-1), which encodes a SOD1, accelerates onset of MND in these mice and induces macrophages to produce high levels of IL-6. We confirm here that ALS patients compared with healthy controls have significantly elevated levels of plasma IL-6 and Interferon-gamma (IFN-γ), but not IL-17. To determine if expression of ATCV-1 SOD1 or SOD1-G93A in mouse macrophages elevates expression of inflammatory cytokines, we transfected the RAW264.7 mouse macrophage cell line with plasmids encoding ATCV-1 SOD1, wild-type human SOD1, SOD1-G93A, or an empty vector. RAW264.7 cells stably expressing wtSOD1 or G93A-SOD1 were stimulated with poly I:C and Interferon-gamma, alone, or in combination to induce inflammatory factors, such as IL-6 and Nitric Oxide (NO), anti-inflammatory factors, such as IL-10, or activation of Interferon Stimulated Response Elements (ISRE) promoters. After stimulation, production of IL-6 and NO, but not IL-10 or ISRE promoter activity was significantly higher in RAW264.7 cells expressing SOD1-G93A compared with wt SOD1. Moreover, RAW264.7 cells expressing SOD1-G93A compared with wt SOD1 produced higher levels of IL-6 and NO in response to ATCV-1 glycoproteins. Finally, transfection of plasmid encoding ATCV-1 SOD1 into RAW264.7 cells significantly increased expression of inflammatory factors in responses to poly I:C and IFN-γ, primarily in an Interferon regulatory factor 3 (IRF3) dependent fashion. These data clearly show that expression of G93A-SOD1 or ATCV-1 SOD1 in macrophages significantly elevates expression of inflammatory factors following stimulations that mimic virus infection, viral components, or T cell cytokines, thereby suggesting one mechanism by which atypical SOD1 in macrophages can contribute to ALS-MND.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152881"},"PeriodicalIF":2.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429614","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":"Regulation of FOXM1 by HDAC3 Inhibition Ameliorates Macrophage Endoplasmic Reticulum stress and Apoptosis in Mycobacterium tuberculosis Infection","authors":"Jinqi Hao,&nbsp;Lan Zhang,&nbsp;Jiafu Qi,&nbsp;Yanqin Yu","doi":"10.1016/j.imbio.2025.152879","DOIUrl":"10.1016/j.imbio.2025.152879","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (Mtb) infection may induce significant damage to the host lung tissues. Endoplasmic reticulum stress (ERS) and apoptosis of macrophages are considered key factors affecting the survival and pathogenicity of intracellular Mtb. Forkhead box M1 (FOXM1) is closely implicated in lung diseases. This study aimed to investigate the role of FOXM1 in Mtb infection and the involvement of histone deacetylase 3 (HDAC3) in this process. An in vitro Mtb infection model was established by infecting RAW264.7 macrophages with Mtb H37Ra. The results showed that RAW264.7 macrophages subjected to Mtb infection showed upregulated expressions of ERS markers and FOXM1. FOXM1 overexpression further elevated the levels of ERS and apoptosis markers, pro-inflammatory cytokines, and reactive oxygen species in Mtb-infected macrophages. FOXM1 could bind to the promoter of <em>TXNIP</em> and activate its transcription. Knockdown of TXNIP suppressed the effects of Mtb infection on macrophages, while upregulation of FOXM1 completely abolished the effects of TXNIP knockdown. HDAC3 inhibitor effectively diminished the effects of FOXM1 upregulation on Mtb-infected macrophages. In conclusion, inhibition of HDAC3 may reduce ERS and apoptosis of Mtb-infected macrophages by regulating the FOXM1/TXNIP axis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152879"},"PeriodicalIF":2.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386539","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":"The Autoimmune Profiles in the Etiopathogenesis of Granulomatous Lobular Mastitis","authors":"Lu Xie,&nbsp;Jiamei Feng,&nbsp;Qingqian Gao,&nbsp;Wenchao Qu,&nbsp;Shijun Shao,&nbsp;Jiaye Sun,&nbsp;Xueqing Wu,&nbsp;Hua Wan","doi":"10.1016/j.imbio.2025.152878","DOIUrl":"10.1016/j.imbio.2025.152878","url":null,"abstract":"<div><h3>Objectives</h3><div>Granulomatous lobular mastitis (GLM) is a chronic breast inflammation with low remission and high recurrence. This study aimed to investigate GLM patients' autoimmune profiles and their correlation with GLM etiopathogenesis.</div></div><div><h3>Methods</h3><div>Samples from GLM patients and fibroadenoma (FA) controls admitted to Shuguang Hospital between July 2021 and July 2022 were analyzed. Patients (107 GLM, 73 FA) underwent humoral immunity (C3, C4, IgG, IgM, IgE and IgA), cellular immunity (CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, regulatory T cells and CD4/CD8 ratio) and cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12 and TNF-α) tests. Immunohistochemical staining (10 GLM, 10 FA normal tissues) detected IL-1β, IL-6, CD86 and CD206, and immunofluorescence (3 GLM, 3 FA normal tissues) evaluated CD86 and CD206 expression. Multivariate analysis was done using logistic regression.</div></div><div><h3>Results</h3><div>GLM featured granulomas with non-caseation necrosis and inflammatory cell infiltration. GLM patients showed higher C3 (<em>P</em> &lt; 0.001), C4 (<em>P</em> &lt; 0.001), IgE (<em>P</em> &lt; 0.05), IgA (<em>P</em> &lt; 0.05), IL-6 (<em>P</em> &lt; 0.001), and IL-8 levels (<em>P</em> &lt; 0.05). M1 (CD86) and M2 (CD206) macrophage markers were significantly higher in GLM than controls in both immunohistochemical and immunofluorescent staining (<em>P</em> &lt; 0.05). The multivariate logistic regression analysis revealed that reproductive history (OR = 7.011, <em>P</em> &lt; 0.01) and C3 expression level (OR = 5565.570, <em>P</em> &lt; 0.001) were independent factors of GLM.</div></div><div><h3>Conclusions</h3><div>The results highlighted the crucial role of elevated M1 and M2 macrophages in GLM inflammation. GLM was associated with reproductive history, C3, C4, IgE, IgA, IL-6, and IL-8, with reproductive history and C3 as independent risks.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152878"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348641","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":"Integrated analyses uncover new features of atypical memory B cells and novel targets for intervention","authors":"Fuli Fan ,&nbsp;Shubei Liu ,&nbsp;Bin Wang ,&nbsp;Xiaojian Song ,&nbsp;Wei Wang","doi":"10.1016/j.imbio.2025.152877","DOIUrl":"10.1016/j.imbio.2025.152877","url":null,"abstract":"<div><h3>Background</h3><div>Atypical memory B (AMB) is a novel subset of B lymphocytes, but its immune features and pathogenetic roles in systemic rheumatic diseases are still largely elusive. This study aimed to characterize transcriptomic features, immune phenotypes and potential signaling pathways of AMB, and also to confirm its alternations in systemic rheumatic diseases via combined transcriptome analyses.</div></div><div><h3>Method</h3><div>B cell subsets and their transcriptomic signatures were identified via analyses of single cell RNA-sequencing (scRNA-seq) data. Functional characterization of AMB was performed with bioinformatics and CyTOF-based phenotyping. Alternation of AMB in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SjS) was evaluated via bioinformatic approaches.</div></div><div><h3>Result</h3><div>A total of 11 B cell subsets including AMB were identified through scRNA-seq transcriptome analyses. Both transcriptome analyses and CyTOF-based immune phenotyping confirmed that AMB had increased levels of TBX21 (T-bet), ITGAX (CD11c), CD19, CD20 and CXCR3 (<em>P</em> &lt; 0.05), and it had decreased expressions of CD27, CD38, CXCR4, CXCR5 and CD62L (P &lt; 0.05). More than 50 % of T-bet⁺ B cells did not express CD11c, and more than 30 % expressed CD27. AMB was characterized by activated mTORC1 signaling and increased p-P38 level (<em>P</em> &lt; 0.05). AMB transcriptional signature was significantly enriched in the peripheral blood and disease tissues of patients of SLE, RA and SjS (P &lt; 0.05), suggesting the expanded AMB cells in those patients.</div></div><div><h3>Conclusion</h3><div>This study defines the transcriptomic signature, immune phenotypes and potential signaling pathways of AMB, and also confirms the involvement of AMB in systemic rheumatic diseases including SLE, RA and SjS via transcriptomic approaches. mTORC1 signaling and P38/MAPK signaling are promising therapeutic targets for systemic rheumatic diseases mediated by AMB.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152877"},"PeriodicalIF":2.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379035","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":"Inhibiting the alternative pathway of complement by reducing systemic complement factor B: Randomized, double-blind, placebo-controlled phase 1 studies with Sefaxersen","authors":"Michael L. McCaleb ,&nbsp;Steven G. Hughes ,&nbsp;Tamar R. Grossman ,&nbsp;Ashley Frazer-Abel ,&nbsp;Bill Jung ,&nbsp;Lixuan Yin ,&nbsp;Scott P. Henry ,&nbsp;Brett P. Monia ,&nbsp;Eugene Schneider ,&nbsp;Richard Geary ,&nbsp;Gary T. Brice","doi":"10.1016/j.imbio.2025.152876","DOIUrl":"10.1016/j.imbio.2025.152876","url":null,"abstract":"<div><div>An over-active alternative complement pathway has been implicated in the pathophysiology of multiple diseases, including IgA nephropathy and geographic atrophy secondary to age related macular degeneration. In first-in-human double-blind, placebo-controlled phase 1 studies, the safety and pharmacodynamic effects of sefaxersen (RO7434656), a GalNAc-conjugated 2’-MOE antisense oligonucleotide targeting the complement factor B mRNA, was investigated. Healthy volunteers received either single or repeated (for 6 weeks) subcutaneous administrations of investigational drug or placebo. Safety and plasma complement protein levels were assessed throughout the studies and during 90-day follow-up periods. All subjects (54) completed the studies and no safety signals or clinically meaningful changes in blood chemistry, urinalysis, hematology, ECG, vital signs or ocular endpoints were observed. Mean levels of systemic complement factor B (FB) were reduced up to 38 % after single administration and 69 % after repeated administration. Lowering of FB protein was paralleled by similar reductions of plasma Bb levels. There was a strong correlation between reduction of plasma levels of FB and alternative complement pathway activity (AH50), but no meaningful changes in classical complement pathway activity (CH50). The long duration of lowering of FB levels following the last dose supports monthly dosing in future clinical trials. These clinical results support the ongoing Phase 2 development for geographic atrophy secondary to age-related macular degeneration and Ph 2/3 development for IgA nephropathy.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152876"},"PeriodicalIF":2.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079426","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":"Qufeng epimedium decoction alleviates rheumatoid arthritis through CYLD-antagonized NF-kB activation by deubiquitinating Sirt1","authors":"Zhiming Wu ,&nbsp;Peng Zhang ,&nbsp;Wenyan Huang ,&nbsp;Yifen Zhou ,&nbsp;Zhengliu Cao ,&nbsp;Chunhong Wu","doi":"10.1016/j.imbio.2025.152875","DOIUrl":"10.1016/j.imbio.2025.152875","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease that markedly limits the patients´ day-to-day functional abilities and life quality. Currently, there is no known cure for RA. Qufeng epimedium decoction, a traditional Chinese medicine, is widely used in China to treat RA. However, its underlying mechanism remains elusive.</div></div><div><h3>Methods</h3><div>The RA animal model was established to investigate the anti-RA effect and regulatory effect on fibroblast-like synoviocytes (FLS) pyroptosis, qRT-PCR, Western blot, flow cytometry, histology staining, and ELISA were utilized to confirm the gene and protein expressions. The interactions between Sirt1 and CYLD were validated through Co-immunoprecipitation (Co-IP) and RNA-FISH assay.</div></div><div><h3>Results</h3><div>Administration with Qufeng epimedium decoction attenuated inflammatory damage, excessive proliferation, and FLSs pyroptosis in an RA rat model. Moreover, treatment of Qufeng epimedium decoction reduced the ubiquitination modification level of Sirt1 in FLSs isolated from an RA rat model. Mechanistically, CYLD, an intermediation for linking Qufeng epimedium decoction and RA, was responsible for Sirt1 deubiquitination to its protein stabilization, thereby deactivating the NF-kB /GSDMD signaling pathway.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that Qufeng epimedium decoction suppresses FLSs pyroptosis and RA progression via CYLD-mediated Sirt1 deubiquitination and deactivation of the NF-kB /GSDMD signaling pathway. This study sheds light on the underlying mechanism of Qufeng epimedium decoction's effectiveness in RA treatment.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152875"},"PeriodicalIF":2.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255635","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":"Precolostral antibody reactivity against Histophilus somni conserved proteins and Escherichia coli whole cells in stillborn and live calves","authors":"Rafał Baran,&nbsp;Joanna Bajzert,&nbsp;Tadeusz Stefaniak,&nbsp;Paulina Jawor","doi":"10.1016/j.imbio.2025.152874","DOIUrl":"10.1016/j.imbio.2025.152874","url":null,"abstract":"<div><div>Recent studies have demonstrated that neither the uterus nor the fetal gastrointestinal tract is sterile. We hypothesized that antibodies (Ab) that react with bacterial antigens are common in fetuses. Plasma samples from 121 stillborn calves were used as the experimental group and 21 live-born healthy calves were used as the control group. In precolostral plasma samples, IgG₁, IgG₂, and IgM Ab reactivity with <em>Histophilus somni</em> rHsp60 and rOMP40 proteins and <em>Escherichia coli</em> whole cells was tested by ELISA. Selected samples from stillborn and live-born calves were evaluated for antibody reactivity with <em>E. coli</em> antigens separated by SDS-PAGE to verify the recognized protein profile. To investigate whether the antibodies were of maternal origin or self-produced, the sera of the dams were evaluated by immunoblotting.</div><div>In calves, positive reactions to all antigens were detected by ELISA. In ELISA, the greatest variation in the results was observed for IgM class reactivity with selected proteins and the <em>E. coli</em> strain. Stillborn calves showed significantly greater reactivity in the IgG₁ subclass with only <em>E. coli</em>. Immunoblotting analysis revealed reactions of IgG₁ and IgM class Ab with <em>E. coli</em> antigens of different molecular weights, both in the control and stillborn groups. The reactivity of the tested calves was not identical to that of their mothers, indicating that the antibodies were self-produced by the calves during pregnancy.</div><div>These results suggest that calves are exposed to different Gram-negative bacteria during pregnancy, and that the stillborn group elicited diverse responses.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152874"},"PeriodicalIF":2.5,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074221","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":"Predictive value and mechanism of lncRNA MANCR for pediatric severe pneumonia via miR-20a-5p / MAPK1 axis","authors":"Yuting Cai ,&nbsp;Jiaxi Xie ,&nbsp;Jinkai Yang","doi":"10.1016/j.imbio.2025.152871","DOIUrl":"10.1016/j.imbio.2025.152871","url":null,"abstract":"<div><div>Severe community-acquired pneumonia (SCAP) significantly threats the safety of children's lives. Long non-coding RNA (lncRNA) MANCR is overexpressed in lung adenocarcinoma (LUAD) tissue, promote the proliferation, invasion, and migration, decreased cell apoptosis of LUAD cells. This study aimed to detect lncRNA MANCR levels in pediatric SCAP, and explore the diagnostic and prognostic significance of MANCR in pediatric SCAP. The mechanism of MANCR was examined in a lipopolysaccharide (LPS)-induced cell model. Serum MANCR level was detected by RT-PCR in participants. The diagnostic and prognostic value of MANCR was analyzed via ROC and KM curves. LPS constructed the pneumonia cell mode. Cell viability and apoptosis were detected by CCK-8 and flow cytometry respectively. ELISA examined the concentration of inflammatory factors. Serum MANCR level was elevated in SCAP patients. High MANCR could predict SCAP from controls (AUC = 0.852, sensitivity = 0.727, specificity = 0.836). High MANCR level is a predictor for poor prognosis of pediatric SCAP (<em>P</em> &lt; 0.001, HR = 5.810, 95 %CI = 2.450–13.781). LPS inhibited cell viability and promoted apoptosis and inflammation of NCI-H1563 cells. Silence of MANCR could promote cell viability, inhibit the cell apoptosis and secretion of CRP, PCT, IL-6, IL-1β, and TNF-α via miR-20a-5p / MAPK1 axis in LPS-stimulated NCI-H1563 cells (<em>P</em> &lt; 0.05). High MANCR levels in pediatric SCAP patients could predict the occurrence and poor prognosis of SCAP. MANCR knockout could inhibit cell apoptosis and inflammatory factors, and enhance cell viability via miR-20a-5p / MAPK1 axis in LPS-stimulated NCI-H1563 cells.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152871"},"PeriodicalIF":2.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046682","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}