Immunological Investigations最新文献

Cathepsin K (CTSK) in Inflammatory and Immune-Mediated Diseases. 组织蛋白酶K （CTSK）在炎症和免疫介导疾病中的作用。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-09 DOI: 10.1080/08820139.2025.2569768

Shiqi Lin, Tao Wang, Changjing Zuo

{"title":"Cathepsin K (CTSK) in Inflammatory and Immune-Mediated Diseases.","authors":"Shiqi Lin, Tao Wang, Changjing Zuo","doi":"10.1080/08820139.2025.2569768","DOIUrl":"https://doi.org/10.1080/08820139.2025.2569768","url":null,"abstract":"Introduction: Cathepsin K (CTSK) is a lysosomal cysteine protease of the papain superfamily. The enzyme plays a key role in bone homeostasis. Immune cells such as dendritic cells, macrophages, and T cells all express CTSK. It modulates inflammation and immunity through NF-κB, TLR, and the RANKL/RANK/OPG axis. Overexpression or underexpression of CTSK appears in rheumatoid arthritis, periodontitis, tumors, and inflammatory bowel disease. Targeted inhibitors and monoclonal antibodies against CTSK are now emerging therapies.Methods: Systematic literature search and critical review of experimental and clinical studies examining CTSK expression, genetic modulation, and targeted inhibition in inflammatory and immune-mediated disease models.Results: Elevated CTSK correlates with disease activity and bone destruction; its inhibition reduces inflammatory cytokines, immune-cell infiltration, and extracellular-matrix degradation. Small-molecule inhibitors (odanacatib, MIV-711, ONO-5334) and biologics attenuate pathology in arthritis, periodontitis, and atherosclerosis.Discussion: CTSK is a promising diagnostic biomarker and therapeutic target, yet its promise hinges on inhibitors that act only where needed, sparing other tissues. Next steps must therefore craft more selective allosteric compounds and test ways to confine them to diseased sites.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-23"},"PeriodicalIF":2.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250975","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}

引用次数: 0

Analysis of the Epigenetic State of the Dm Element within the Igκ Locus in Pre-B Cells. 前b细胞Igκ位点Dm元件的表观遗传状态分析。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-07 DOI: 10.1080/08820139.2025.2570490

Caijun Wu, Yanying Dong, Wen Zhou, Yingjun Wang, Xing Wang, Ziling Zhao, Yanhong Ji

{"title":"Analysis of the Epigenetic State of the Dm Element within the Igκ Locus in Pre-B Cells.","authors":"Caijun Wu, Yanying Dong, Wen Zhou, Yingjun Wang, Xing Wang, Ziling Zhao, Yanhong Ji","doi":"10.1080/08820139.2025.2570490","DOIUrl":"https://doi.org/10.1080/08820139.2025.2570490","url":null,"abstract":"Background: The Igκ locus undergoes multiple molecular processes during B cell development, including V(D)J recombination and epigenetic regulation, which are influenced by cis-regulatory regions within the locus. A novel cis-regulatory region, termed the Dm element, has been identified. It functions in coordination with the 3'Eκ and Ed enhancers and has been implicated in Igκ demethylation and somatic hypermutations (SHM). The Dm element is characterized by a high density of CpG dinucleotides, a hallmark of region subject to DNA methylation. Our previous work demonstrated that RAG2, but not RAG1, contributes to the Igκ locus demethylation. However, whether RAG proteins influence the epigenetic state of the Dm element remains unknown.Methods: Here, we investigated the epigenetic state of the Dm element using bisulfite sequencing and chromatin immunoprecipitation (ChIP).Results: We found that the Dm element was hypermethylated in pre-B cells but partially demethylated in splenic B cells. Furthermore, it was marked by active histone modifications, including H3K27Ac and H3K9Ac, and was bound by B cell-specific transcription factor Pax5 in pre-B cells.Conclusion: Our findings provide evidence that the Dm element undergoes DNA methylation remodeling in mature B cells, potentially contributing to Igκ allelic expression.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-15"},"PeriodicalIF":2.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238593","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}

引用次数: 0

PD-1/TIM-3-Expressing Myeloid Cells During the Early Immune Reconstitution in Patients with Multiple Myeloma After High-Dose Chemotherapy. PD-1/ tim -3在多发性骨髓瘤患者高剂量化疗后早期免疫重建中的表达

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-04 DOI: 10.1080/08820139.2025.2568871

Polina A Serpeninova, Tamara V Tyrinova, Egor V Batorov, Marina A Tikhonova, Tatyana A Aristova, Daria S Batorova, Svetlana A Sizikova, Galina Yu Ushakova, Vera V Denisova, Elena R Chernykh

{"title":"PD-1/TIM-3-Expressing Myeloid Cells During the Early Immune Reconstitution in Patients with Multiple Myeloma After High-Dose Chemotherapy.","authors":"Polina A Serpeninova, Tamara V Tyrinova, Egor V Batorov, Marina A Tikhonova, Tatyana A Aristova, Daria S Batorova, Svetlana A Sizikova, Galina Yu Ushakova, Vera V Denisova, Elena R Chernykh","doi":"10.1080/08820139.2025.2568871","DOIUrl":"https://doi.org/10.1080/08820139.2025.2568871","url":null,"abstract":"Background: In multiple myeloma (MM), immune checkpoint blockade is being explored as a treatment strategy. However, the role of inhibitory checkpoint receptors on myeloid cells remains poorly understood. The aim of our study was to investigate the expression of PD-1 and TIM-3 on monocytes and monocytic myeloid-derived suppressor cells (M-MDSCs) and their contribution to early immune reconstitution.Methods: The count of monocytic cells and expression of PD-1 and TIM-3 was assessed by flow cytometry.Results: At the engraftment, monocyte subsets counts were similar to pre-transplant values, while the relative content of M-MDSCs was significantly higher. The frequencies of TIM-3-positive cells among intermediate and non-classical monocytes were significantly increased. Incubation of mononuclear cells of MM patients in remission with homeostatic cytokines led to a significant increase in intermediate monocytes and a trend to an increase in the M-MDSCs count and stimulated the expression of PD-1 and TIM-3. PD-1 and TIM-3 expression on monocytes and M-MDSCs inversely correlated with lymphocyte count at the engraftment. TIM-3 expression on monocytic cells was associated with regulatory T-cell count. After auto-HSCT, PD-1/TIM-3-expressing cells exhibited significantly elevated IL-10 production (with decreased TNFα production).Conclusion: PD-1 and TIM-3 on monocytic cells may play a significant role in immune reconstitution.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-23"},"PeriodicalIF":2.4,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225145","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}

引用次数: 0

Profiling of Epstein-Barr Virus microRNAs in Whole Blood and Exosomes in Multiple Sclerosis. 多发性硬化症患者全血和外泌体Epstein-Barr病毒microrna的分析

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 DOI: 10.1080/08820139.2025.2559799

Victoria Hyslop Hvalkof, Anna Gabriella Stenvig Olsson, Stefan Gustavsen, Annika Reynberg Langkilde, Malene Bredahl Hansen, Finn Sellebjerg, Helle Bach Søndergaard

{"title":"Profiling of Epstein-Barr Virus microRNAs in Whole Blood and Exosomes in Multiple Sclerosis.","authors":"Victoria Hyslop Hvalkof, Anna Gabriella Stenvig Olsson, Stefan Gustavsen, Annika Reynberg Langkilde, Malene Bredahl Hansen, Finn Sellebjerg, Helle Bach Søndergaard","doi":"10.1080/08820139.2025.2559799","DOIUrl":"https://doi.org/10.1080/08820139.2025.2559799","url":null,"abstract":"Background: Multiple sclerosis (MS) is a neuroinflammatory, demyelinating disease with Epstein-Barr virus (EBV) suggested as a prerequisite for disease development. EBV expresses 44 microRNAs (miRNAs) with largely unknown functions, but they have been implicated in EBV-infected cell proliferation and immune evasion.Objectives: This study investigates EBV miRNAs levels in whole blood and plasma exosomes at baseline and after treatment, and in relation to disease activity based on age-adjusted NfL ratios, in 50 newly diagnosed patients with relapsing-remitting MS (RRMS).Methods: EBV miRNAs purified from whole blood and isolated plasma exosomes were measured by qPCR, using TaqMan Array Cards, and correlated to mRNA of GZMA, GZMH, IFN-γ, TNF-α, IL-10, IL-1B, and IL-1R1 in whole blood, measured by qPCR. Serum neurofilament light chain (NfL) and IL-6, plasma anti-EBNA1 antibody titers, occludin, and zonula occludens-1 were measured by various immunoassays.Results: The miRNA profiling of whole blood revealed expression of BHRF1 miRNAs in most patients, indicating that EBV is in lytic phase or latency phase III. Higher levels of miR-BART14-3p were observed in patients classified with high disease activity. EBV miRNA levels correlated with anti-EBNA1 antibody titers, biomarkers of inflammation and tight junction proteins.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-18"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199203","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}

引用次数: 0

Differential Methylation Patterns Predict HBsAg Seroconversion in Hepatitis B Virus Reactivation Patients. 不同甲基化模式预测乙型肝炎病毒再激活患者HBsAg血清转化。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-07-21 DOI: 10.1080/08820139.2025.2532630

Jayesh Kumar Sevak, Mojahidul Islam, Gayantika Verma, Anoushka Saxena, Preedia Babu E, Shahana Parveen, Ankur Jindal, Manoj Kumar Sharma, Gayatri Ramakrishna, Syed Naqui Kazim, Shiv Kumar Sarin, Nirupama Trehanpati

{"title":"Differential Methylation Patterns Predict HBsAg Seroconversion in Hepatitis B Virus Reactivation Patients.","authors":"Jayesh Kumar Sevak, Mojahidul Islam, Gayantika Verma, Anoushka Saxena, Preedia Babu E, Shahana Parveen, Ankur Jindal, Manoj Kumar Sharma, Gayatri Ramakrishna, Syed Naqui Kazim, Shiv Kumar Sarin, Nirupama Trehanpati","doi":"10.1080/08820139.2025.2532630","DOIUrl":"10.1080/08820139.2025.2532630","url":null,"abstract":"Background: Hepatitis B virus (HBV) modulates immune epigenetic landscape. Therefore, we investigated immune epigenetic landscape in HBsAg seroconverters and non-seroconverters.Methods: Sixteen rHBV patients including seroconverters (SC, n = 7) and non-seroconverters (NSC, n = 9) at baseline and week 24 were recruited. Age matched naïve chronic hepatitis B patients (nCHBV, n = 7) and healthy controls (HC, n = 6) were also included. PBMCs and plasma were subjected to genome-methylation, gene-expression, immunophenotyping, functionality, and cytokines analysis using Reduced Representation Bisulfite Sequencing (RRBS), qRT-PCR, flow-cytometry, and cytokine-bead-array.Results: In rHBV patients, as compared to nCHBV, there is significant hypomethylation (p < .05) of epigenetic remodellers and immune and metabolic genes like KDM2B, NCOR2 and GATA6, TGF-β, IL-6, IRF8, RPTOR, HK3, specifically at CpG islands. At baseline, HBsAg SC had hypomethylation of KDM2B, COX19, IRF8, TLR5, and hypermethylation of LAG3 compare to NSC. By week-24, SC demonstrated hypomethylation of IL17RA, IFN-γ, TGF-β, STAT5B (p < .05) and correlated with increased plasma IL-6 (p = .009) and decreased LAG3 (p = .01). At baseline and 24 weeks, SC depicted differentiation of HBV-specific CD8+, Tfh, and Th1/17 cells.Conclusion: This study identifies hypomethylation of immune genes suggesting enhanced immune response and viral clearance in SC. Conversely, nCHBV and NSC consistently exhibited hypomethylation of LAG3 and TOX, contributing to immune exhaustion.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1220-1240"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674667","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}

引用次数: 0

Psoriasis Relapse: Exploring the Role of Epigenetics, Metabolic Reprogramming, and Inflammatory Memory. 银屑病复发：探索表观遗传学、代谢重编程和炎症记忆的作用。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-06-19 DOI: 10.1080/08820139.2025.2519666

Sakshi Wadhavane, Arulkumaran Rithvik, Mahaboobkhan Rasool

{"title":"Psoriasis Relapse: Exploring the Role of Epigenetics, Metabolic Reprogramming, and Inflammatory Memory.","authors":"Sakshi Wadhavane, Arulkumaran Rithvik, Mahaboobkhan Rasool","doi":"10.1080/08820139.2025.2519666","DOIUrl":"10.1080/08820139.2025.2519666","url":null,"abstract":"Background: Psoriasis is a chronic autoimmune condition characterized by recurrent episodes of skin inflammation. Despite progress in treatment, managing flare-ups of psoriasis remains a significant hurdle once the therapy is halted. This review aims to unravel the enigma of relapse by examining the interactions between epigenetics, metabolic reprogramming, and inflammatory memory.Methods and results: Skin-resident memory T cells and keratinocytes with a history of inflammation play crucial roles in the metabolic and epigenetic alterations observed during relapse. This review explores epigenetic factors involved in the recurrence of psoriasis, such as histone alterations, chromatin restructuring, and non-coding RNAs. Furthermore, we explored environmental influences, metabolic reprogramming, and genetic predispositions that influence the persistence and recurrence of psoriasis. We also outline the function of the gut-brain-skin axis in this scenario. Finally, we discuss pharmacological strategies for managing psoriasis relapse, including targeted biologics.Conclusion: This review provides a comprehensive summary on the intricate epigenetic, molecular, metabolic and environmental cues that exacerbate or facilitate psoriasis relapse. In summary, it also provides an enticing update on the therapeutics currently employed to treat psoriasis relapse.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"935-961"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325573","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}

引用次数: 0

Association between UBQLN Family Gene and Systemic Lupus Erythematosus: A Case Control Study. UBQLN家族基因与系统性红斑狼疮的关系：一项病例对照研究

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-07-08 DOI: 10.1080/08820139.2025.2530726

Qing Wu, Yong Liu, Xinyi Zhao, Qin Zhang

{"title":"Association between UBQLN Family Gene and Systemic Lupus Erythematosus: A Case Control Study.","authors":"Qing Wu, Yong Liu, Xinyi Zhao, Qin Zhang","doi":"10.1080/08820139.2025.2530726","DOIUrl":"10.1080/08820139.2025.2530726","url":null,"abstract":"Objective: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder. This study aims to investigate the association between UBQLN family genes and the systemic lupus erythematosus (SLE).Methods: In the present study, plasma levels of UBQLN family genes were evaluated in 113 SLE patients and 115 healthy controls. The relative mRNA expression levels of UBQLN family genes in peripheral blood lymphocytes were quantified using qRT-PCR. Additionally, UBQLN protein levels in serum were measured using enzyme-linked immunosorbent assay (ELISA). The diagnostic potential of UBQLN family genes was evaluated by calculating the area under the receiver operating characteristic (ROC) curve. Correlation analysis was conducted using Pearson and Spearman methods, while logistic regression was employed for one-way analysis.Results: The mRNA expression levels of UBQLN4 and UBQLN2 SLE patients were significantly lower than those in the control group (both p < .05). Moreover, the combined diagnostic performance of UBQLN4 and UBQLN2 surpassed that of each gene alone, with a combined AUC of 0.697. The protein expression levels of UBQLN1, UBQLN2, and UBQLN4 were also significantly reduced in SLE patients compared to controls (all p < .05).Conclusion: These findings suggest that UBQLN family genes in peripheral blood lymphocytes may play a role in the pathogenesis of SLE and hold promise as biomarkers for the diagnosis and treatment of the disease.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1210-1219"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583817","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}

引用次数: 0

Differences in Aqueous Humor Cytokine Concentrations According to the Presence of Posterior Subcapsular Cataract: A Prospective Case-Control Study. 后囊膜下白内障存在时房水细胞因子浓度的差异：一项前瞻性病例对照研究。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-05-29 DOI: 10.1080/08820139.2025.2512143

Kyu Seong Jo, Ji Eun Song, Yongwoo Lee

{"title":"Differences in Aqueous Humor Cytokine Concentrations According to the Presence of Posterior Subcapsular Cataract: A Prospective Case-Control Study.","authors":"Kyu Seong Jo, Ji Eun Song, Yongwoo Lee","doi":"10.1080/08820139.2025.2512143","DOIUrl":"10.1080/08820139.2025.2512143","url":null,"abstract":"Background: Posterior subcapsular cataract (PSC) substantially impacts visual function, and prior studies have suggested that inflammatory cytokines may have a role in its development. We aimed to analyze inflammatory cytokine concentrations in the aqueous humor by cataract type and severity, specifically comparing them in relation to the presence of PSC, and to identify risk factors for PSC.Methods: We prospectively recruited patients undergoing routine cataract surgery. PSC presence was documented via slit-lamp examination and anterior segment photography during cataract diagnosis. Aqueous humor samples were collected prior to surgery and analyzed using quantitative multiplexed antibody assays to measure the concentrations of 10 inflammatory cytokines (interferon-α [IFN-α], IFN-γ, interleukin [IL]-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, and tumor necrosis factor-α). Cytokine concentrations were compared according to PSC status.Results: Overall,80 eyes of 80 patients were included, 45 with and 35 without PSC. Compared with those in the non-PSC group, patients with PSC showed significantly higher aqueous humor concentrations of IFN-γ (2.764 vs. 2.301 pg/mL, p = .013). No significant correlation was observed between PSC status and the aqueous humor concentrations of other examined inflammatory cytokines.Conclusion: IFN-γ expression tended to be higher in eyes with PSC than in those without PSC, suggesting a possible role in PSC pathophysiology.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1099-1109"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181111","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}

引用次数: 0

Hypoxic ADSC Exosomes Alleviate Primary Sjögren's Syndrome-Induced Skin Injury via GLRX2 Delivery and Ferroptosis Suppression. 缺氧ADSC外泌体通过GLRX2传递和抑制铁下沉减轻原发性Sjögren综合征诱导的皮肤损伤。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-06-10 DOI: 10.1080/08820139.2025.2516671

Xin Wang, Fengjiao Wu, Xinmeng Yang, Huimin Yang, Guixia Xu, Ruilian Chen, Qinqin Xiang, Mingming Jin, Chao Sun

{"title":"Hypoxic ADSC Exosomes Alleviate Primary Sjögren's Syndrome-Induced Skin Injury via GLRX2 Delivery and Ferroptosis Suppression.","authors":"Xin Wang, Fengjiao Wu, Xinmeng Yang, Huimin Yang, Guixia Xu, Ruilian Chen, Qinqin Xiang, Mingming Jin, Chao Sun","doi":"10.1080/08820139.2025.2516671","DOIUrl":"10.1080/08820139.2025.2516671","url":null,"abstract":"Background: The aim of the present study was to assess the therapeutic effects of ADSC-Exos for SS-induced skin injury.Methods: A mouse model of SS was constructed and Exos from ADSCs (Exos) and hypoxia-pretreated ADSCs (HExos) were isolated. The therapeutic effects of Exos were identified using an enzyme-linked immunosorbent assay, immunohistochemistry, and immunofluorescence. High-throughput sequencing (HTS) was employed to identify differentially expressed genes between ADSC-Exos and ADSC-HExos. The results showed that treatment with ADSC-Exos, especially ADSC-HExos, inhibited SS-induced expression of inflammatory factors, ferroptosis, and deposition of reactive oxygen species.Results: The results of HTS and polymerase chain reaction analysis revealed that GLRX2 plays an important role in protected effects of ADSC-HExo against SS-induced skin injury. In vitro analysis usingHaCaT cells confirmed that GLRX2 inhibited lipopolysaccharide-induced skin injury by inhibiting ferroptosis, as confirmed with the ferroptosis inhibitorFerrostatin-1. GLRX2 upregulation increased the therapeutic effects of ADSC-Exos against skin injury of SS mice.Conclusion: Moreover,ADSC-HExos effectively promoted collagen I expression, suggesting that ADSC-HExos attenuated primary SS-induced skin injury via GLRX2 delivery and ferroptosis suppression.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1126-1137"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258006","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}

引用次数: 0

M2 Polarization of RAW264.7-Derived Exosomes Inhibits Osteoclast Differentiation and Inflammation via PKM2/HIF-1α Axis. raw264.7衍生外泌体的M2极化通过PKM2/HIF-1α轴抑制破骨细胞分化和炎症。

IF 2.4 4区医学

Immunological Investigations Pub Date : 2025-10-01 Epub Date: 2025-06-29 DOI: 10.1080/08820139.2025.2525896

Yue Zhang, Yufu Liang, Yue Zhou

{"title":"M2 Polarization of RAW264.7-Derived Exosomes Inhibits Osteoclast Differentiation and Inflammation via PKM2/HIF-1α Axis.","authors":"Yue Zhang, Yufu Liang, Yue Zhou","doi":"10.1080/08820139.2025.2525896","DOIUrl":"10.1080/08820139.2025.2525896","url":null,"abstract":"Background: Periodontitis (PD) is a chronic inflammatory disease characterized by alveolar bone loss, primarily driven by excessive osteoclast differentiation and activation. Exosomes derived from M2 macrophages have been implicated in the pathological progression of various diseases, including PD. Pyruvate kinase (PK)M2, a key metabolic enzyme, promotes inflammation in periodontal disease through enhanced production of pro-inflammatory cytokines. This study investigated whether M2 macrophage-derived exosomes regulate osteoclast differentiation and contribute to PD progression.Methods: Exosomes were isolated from M2-polarized RAW264.7 cells. Osteoclast differentiation was induced in M2-polarized RAW264.7 cells through treatment with receptor activator of nuclear factor kappa-B ligand (RANKL). Reverse transcription quantitative PCR (RT-qPCR) was used to analyze mRNA levels of osteoclast differentiation-related genes. Enzyme-linked immunosorbent assay (ELISA) quantified inflammatory cytokine production. Co-immunoprecipitation assays were performed to detect the interaction between PKM2 and hypoxia-inducible factor-1α (HIF-1α). To inhibit or activate PKM2 activity, RAW 264.7 cells were treated with Shikonin or TEPP46.Results: Exosomes were successfully extracted from RAW264.7 cells. M2-derived exosomes significantly suppressed RANKL-induced osteoclast differentiation and inflammatory responses. Furthermore, these exosomes modulated the PKM2/HIF-1α signaling axis. Shikonin treatment inhibited RANKL-induced osteoclastogenesis and inflammation, whereas TEPP46 treatment enhanced these processes.Conclusion: The M2 polarization of RAW264.7-derived exosomes inhibits osteoclast differentiation and inflammation through the PKM2/HIF-1α pathway, providing potential insights into the molecular mechanisms underlying PD pathogenesis.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1195-1209"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527754","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}

引用次数: 0