Immunobiology最新文献

{"title":"Suppression of astrocyte elevated gene-1 protects against light-induced photoreceptor apoptosis and inflammation in retina","authors":"Xinran Gao ,&nbsp;Haoran Qiao","doi":"10.1016/j.imbio.2025.152889","DOIUrl":"10.1016/j.imbio.2025.152889","url":null,"abstract":"<div><h3>Purpose</h3><div>To research the function of astrocyte elevated gene-1 (AEG-1) in light-induced retinal degeneration.</div></div><div><h3>Methods</h3><div>The retinas of BALB/c mice and 661W cells damage were induced by exposure to light; Lipopolysaccharide (LPS) was used to stimulate BV2 cells. AEG-1 siRNA transfection was used to inhibit AEG-1. Expressions of AEG-1, TLR4, TNF-α, phosphor-NF-κB (p-NF-κB) and total NF-κB (t-NF-κB) were detected. Photoreceptor apoptosis was evaluated by flow cytometry or TUNEL. Histological analyses were performed by hematoxylin and eosin (HE) staining.</div></div><div><h3>Results</h3><div>AEG-1 was highly expressed in light damaged (LD) retinas. The photoreceptor apoptosis and the thinning of outer nuclear layer (ONL) were inhibited by AEG-1 siRNA in LD mice retinas. The AEG-1 siRNA pretreatment significantly down-regulated the elevated expression levels of TLR4, p-NF-κB and TNF-α induced by LD in retinas. In vitro, AEG-1 was upregulated in 661W cells induced by LD and in BV2 cells stimulated by LPS. The AEG-1 siRNA prevented light induced apoptosis of 661W cells, and down-regulated the elevated expressions of TLR4, p-NF-κB and pro-inflammatory cytokine TNF-α caused by LPS in BV2 cells.</div></div><div><h3>Conclusions</h3><div>AEG-1 is highly expressed in retinal degeneration caused by LD. Suppression of AEG-1 protects against photoreceptor apoptosis and rescues the thinning of ONL in LD retinas. Suppression of AEG-1 also diminishes inflammation in light induced retinal degeneration, which may be regulated through the NF-κB pathway. Therefore, AEG-1 perhaps become a potential therapeutic target for this type of retinal degenerative disease.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152889"},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636941","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":"Assessment of cellular immune phenotype of peripheral blood mononuclear cells in Bangladeshi children with severe acute malnutrition","authors":"Zannatun Noor ,&nbsp;Shaumik Islam ,&nbsp;Md. Mehedi Hasan ,&nbsp;Ar-Rafi Khan ,&nbsp;Md Amran Gazi ,&nbsp;Farzana Hossaini ,&nbsp;Rashidul Haque ,&nbsp;Tahmeed Ahmed ,&nbsp;Mustafa Mahfuz","doi":"10.1016/j.imbio.2025.152887","DOIUrl":"10.1016/j.imbio.2025.152887","url":null,"abstract":"<div><div>Children suffering from severe acute malnutrition (SAM) have a weakened immune system. The relationship between malnutrition and alterations in the frequency of peripheral blood mononuclear cells (PBMCs) remains unclear. This study investigated the altered immune responses in Bangladeshi children with SAM compared to healthy children. PBMCs were collected from 24 healthy children and 25 children with SAM upon their hospital admission and after 21 days of nutritional therapy at a nutritional rehabilitation unit. Flow cytometry was employed to assess various subsets of T cells, B cells, and natural killer (NK) cells. Children with SAM exhibited significantly lower levels of activated (CD25+) B cells (SAM vs. healthy: 0.18 % vs. 0.30 %, <em>p</em> = 0.031) and NK cells (SAM vs. healthy: 4.9 % vs. 9.6 %, <em>p</em> = 0.003) compared to healthy controls. Similar immune responses were observed in SAM children during both hospitalization and discharge, with NK cell percentages showing slight increases but remaining significantly lower than in healthy children (SAM endline vs. healthy: 5.9 % vs. 9.6 %, <em>p</em> = 0.032). Notable reductions were also observed in CD62+ helper T cells, CD62L+ cytotoxic T cells, and CD62L+ B cells. These results suggest that although SAM children recover clinically, their immune systems remain compromised during discharge.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152887"},"PeriodicalIF":2.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610287","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":"Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients","authors":"Yin-hong Zhang ,&nbsp;Juan Chen ,&nbsp;Wen-fei Mao ,&nbsp;Li-xi Yan ,&nbsp;Fei Long ,&nbsp;Sheng-hao Li ,&nbsp;Rui-xian Zhang","doi":"10.1016/j.imbio.2025.152885","DOIUrl":"10.1016/j.imbio.2025.152885","url":null,"abstract":"<div><h3>Background</h3><div>Systemic Lupus Erythematosus (SLE) is an autoimmune disorder marked by an imbalance between pro-inflammatory Th17 cells and regulatory T cells (Tregs), which contributes to chronic inflammation and multi-organ damage, necessitating novel therapeutic strategies.</div></div><div><h3>Methods</h3><div>This study investigates the potential of adipose-derived stem cell (ADSC) exosomes to modulate the Th17/Treg balance in SLE patients through the miR-16-5p/LATS1 axis. Flow cytometry, ELISA, and quantitative real-time PCR were utilized to assess immune cell populations and cytokine levels in SLE patients. Additionally, ADSC exosomes were isolated and characterized, and their impact on CD4+ T cells was evaluated using dual-luciferase and Western blot assays.</div></div><div><h3>Results</h3><div>SLE patients exhibited increased Th17 cells and decreased Tregs, with corresponding changes in cytokine levels. Reduced miR-16-5p expression was noted in CD4+ T cells, correlating positively with Treg proportions. ADSC-derived exosomes were shown to deliver miR-16-5p effectively, targeting and downregulating LATS1 expression. This modulation restored the Th17/Treg balance and adjusted cytokine expression, indicating an immune regulatory effect.</div></div><div><h3>Conclusion</h3><div>ADSC-derived exosomes, through the miR-16-5p/LATS1 axis, offer a promising therapeutic approach for SLE by restoring immune equilibrium. This study highlights the potential of exosome-based therapies in modulating immune responses, providing a foundation for developing innovative treatments for autoimmune diseases.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152885"},"PeriodicalIF":2.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580566","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":"Unveiling the Role of Oligosaccharyltransferase STT3B in Colorectal Cancer Tissues: Clinical significance and Molecular Mechanisms Driving the Formation of Tertiary Lymphoid Structures","authors":"Caixia Zhang ,&nbsp;Bin Wang ,&nbsp;Xiaofeng Bian ,&nbsp;Youcai Zhao ,&nbsp;Xiaobing Yang ,&nbsp;Wei Zhao","doi":"10.1016/j.imbio.2025.152886","DOIUrl":"10.1016/j.imbio.2025.152886","url":null,"abstract":"<div><div>The role of tertiary lymphatic structures (TLS) in anti-tumor response has garnered increasing attention; however, the clinical implications and regulatory mechanisms of various TLS subtypes remain poorly understood. This study investigates the function of the oligosaccharyltransferase subunit STT3B in modulating TLS formation and B cell activity within colorectal cancer (CRC) tissues. Spatial morphology analysis was employed to accurately identify the localization of STT3B expression within TLS. By integrating clinical samples with bioinformatics analyses, we examined the expression levels and distribution patterns of STT3B in the CRC microenvironment and assessed its clinical significance. Transcriptome sequencing, combined with <em>in vitro</em> validation, was utilized to evaluate the effects of STT3B knockdown on B cell functionality. The findings indicated that CRC patients with a high density of STT3B expression in the TLS had a better prognosis. Multicolor fluorescence analysis further demonstrated that the density of STT3B⁺CD19⁺ B cells correlated with pathological characteristics and lymph node metastasis status in CRC patients, with higher densities predicting longer disease-free survival. Transcriptome sequencing further demonstrated that STT3B knockdown predominantly impacts B cell metabolic functions. <em>In vitro</em> experiments confirmed that the downregulation of STT3B inhibits the metabolism and proliferation of B cells. These findings suggest that STT3B plays a crucial role in enhancing B cell metabolism and facilitating the development of mature TLS, which is associated with improved prognostic outcomes in patients with CRC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152886"},"PeriodicalIF":2.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562699","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":"Renqing Changjue alleviates sepsis-induced acute lung injury by regulating renin-angiotensin system and inhibiting inflammatory response","authors":"Minxia Zhu ,&nbsp;Yaqi Lei ,&nbsp;Zhaojun Zhang ,&nbsp;Xu Guo ,&nbsp;Jing Guo ,&nbsp;Ruipeng Wu ,&nbsp;Xiaofeng Li ,&nbsp;Shibo Tian ,&nbsp;Yuanhao Zhao","doi":"10.1016/j.imbio.2025.152883","DOIUrl":"10.1016/j.imbio.2025.152883","url":null,"abstract":"<div><div>Sepsis, with high morbidity and mortality, represents a systemic inflammatory response syndrome. A common consequence of sepsis is acute lung injury (ALI). Renqing Changjue (RQCJ), a renowned prescription in traditional Tibetan medicine, is reported to have anti-inflammatory effects. The present study was aimed at exploring whether RQCJ could mitigate sepsis-induced ALI and elucidating its underlying mechanism. The rat model of sepsis-induced ALI was established by intraperitoneal injection of lipopolysaccharide (LPS), and high, medium, and low doses of RQCJ were administered. The results indicated that the intervention of RQCJ improved septic symptoms, mitigated the murine sepsis score and pulmonary edema in LPS-induced septic rats, and decreased inflammatory cytokines in lung tissue such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Furthermore, RQCJ regulated the balance of renin-angiotensin system by enhancing the enzyme activity of angiotensin converting enzyme 2 (ACE2) while inhibiting ACE, thereby promoting the production of angiotensin 1–7 (Ang1–7). This study highlights the multiple protective effects of RQCJ on sepsis-induced ALI, providing a valuable reference for its further development and offering a novel perspective for the treatment of sepsis-induced ALI.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152883"},"PeriodicalIF":2.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520106","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":"CVB3 regulates Treg cell pyroptosis through the lncRNA XIST/miR-195-5p/caspase-1 molecular axis","authors":"Yan Zhang ,&nbsp;Lei Yang ,&nbsp;Huiting Mu ,&nbsp;Na Li ,&nbsp;Xuejia Wang ,&nbsp;Hualan Lei ,&nbsp;Mingjie Pang","doi":"10.1016/j.imbio.2025.152882","DOIUrl":"10.1016/j.imbio.2025.152882","url":null,"abstract":"<div><div>Viral myocarditis (VMC) is characterized by severe cardiac inflammation and is a major cause of congestive heart failure and sudden cardiac death in healthy young people. The lncRNA XIST plays an important regulatory role in myocardial injury, but its role in VMC caused by coxsackievirus B3 (CVB3) infection is unclear. In this study, we evaluated the effects of the lncRNA XIST on a CVB3-induced VMC mouse model and on pyroptosis in CVB3-exposed Treg cells. The results showed that in CVB3-infected VMC and Treg cells, the expression level of the lncRNA XIST was increased, whereas miR-195-5p expression was decreased. In CVB3-induced VMC mice, inflammation was elevated, whereas the Treg/Th17 ratio was reduced. Knocking down the lncRNA XIST suppressed pyroptosis in Treg cells caused by CVB3 infection and inhibited VMC progression in vivo. Studies on downstream mechanisms have shown that the lncRNA XIST targets miR-195-5p, induces caspase-1 expression through the inhibition of miR-195-5p, promotes the expression of the inflammatory factors IL-1β and IL-18 associated with pyroptosis, inhibits the secretion of the anti-inflammatory factors IL-10 and TGF-β1, and ultimately promotes pyroptosis in Treg cells. In conclusion, knocking down the lncRNA XIST inhibits CVB3-induced pyroptosis of Treg cells and VMC progression in mice induced by CVB3 infection. These findings provide a potential theoretical basis for the treatment of VMC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 2","pages":"Article 152882"},"PeriodicalIF":2.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471236","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":"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}