Molecular immunology最新文献

{"title":"Fecal metabolomics in Crohn’s disease reveal N-Acetylglutamine as a Th17/Treg modulator","authors":"Meijuan Han ,&nbsp;Xuetao Dong ,&nbsp;Ruxin Zhao ,&nbsp;Xiao Hu ,&nbsp;Dan Li ,&nbsp;Xinchen Yan ,&nbsp;Yandi Liu ,&nbsp;Qiupeng Du ,&nbsp;Muran Li","doi":"10.1016/j.molimm.2025.11.012","DOIUrl":"10.1016/j.molimm.2025.11.012","url":null,"abstract":"<div><div>The gut microbiota is widely recognized as a key component in the pathogenesis of inflammatory bowel disease (IBD), and one of its primary modes of interaction with the host occurs via metabolites. Studies have confirmed that gut microbiota dysbiosis affects immune maturation, immune homeostasis, host energy metabolism, and the maintenance of mucosal integrity. However, the specific metabolites that influence the differentiation of mucosal CD4⁺ T cells remain insufficiently elucidated. This study aimed to identify and validate unknown metabolites capable of affecting the differentiation of CD4⁺ T cell subsets by characterizing changes in fecal metabolites between IBD patients and non-IBD controls. Using untargeted metabolomics, we quantitatively detected a total of 1480 metabolites in positive ion mode and 1178 metabolites in negative ion mode. Regression analysis results showed that N-Acetylglutamine was significantly downregulated in IBD patients and was identified as a key differential metabolite. Further in vitro functional experiments confirmed that this metabolite could directly regulate the differentiation balance of CD4⁺ T cells, specifically inhibiting the differentiation of pathogenic Th17 (pTh17) cells while promoting the generation of Treg. This study verifies the critical role of the metabolite N-Acetylglutamine in regulating the Treg/pTh17 cell balance, providing a theoretical basis for its potential as a therapeutic target for IBD.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 82-97"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxic conditioning induced by CoCl2 enhanced the therapeutic effects of mesenchymal stem cell-derived exosomes on oxazolone-induced atopic dermatitis-like skin lesions in BALB/c mice","authors":"Jin-Woo Kim ,&nbsp;Hyeon Ji Lee ,&nbsp;Pahn-Shick Chang ,&nbsp;Jung Min Lee ,&nbsp;Jin-Chul Kim","doi":"10.1016/j.molimm.2025.12.008","DOIUrl":"10.1016/j.molimm.2025.12.008","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is a chronic skin disease characterized by inflammation and disruption of the skin barrier. It is normally treated using moisturizers and steroids; however, these are palliatives and do not serve as a therapy. Mesenchymal stem cells (MSCs) are tissue stem cells with immunomodulatory activities, and exosomes reflect the physiologies of producer cells. Therefore, the use of MSCs and exosomes with their immunomodulatory activities is emerging as a new method to treat AD. Here, we used cobalt chloride (CoCl₂) to induce hypoxic conditioning, and tested the therapeutic efficacy of exosomes derived from CoCl₂-treated MSCs in treating AD. <em>In vitro</em>, the exosomes derived from CoCl₂-treated MSCs increased the proliferation of HaCaT cells and decreased inflammatory cytokine levels. In the oxazolone-induced chronic AD mouse model, the exosomes derived from CoCl₂-treated MSCs reduced ear thickness, restored the skin barrier, and reduced immune cell infiltration and inflammatory markers. These data indicated that hypoxic conditioning induced by the CoCl₂ treatment enhanced the therapeutic efficacy of exosomes derived from MSCs, suggesting that these exosomes can be used to alleviate the symptoms of AD. Given the current AD treatment landscape dominated by biologics and JAK inhibitors, our approach may serve as a steroid-sparing, biologic-agnostic adjunct or alternative, leveraging the safety and manufacturability of cell-free therapy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"189 ","pages":"Pages 153-162"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the lambda light chain repertoire and non-coding regions of equine immunoglobulins using the EquCab3 genome","authors":"Glória Maria da Silva ,&nbsp;Carlena Navas ,&nbsp;Milene Barbosa Carvalho ,&nbsp;Yala Sampaio ,&nbsp;Marcele Neves Rocha ,&nbsp;Adriano Gomes-Silva ,&nbsp;Herbert L. de Matos Guedes ,&nbsp;Luiz Cunha ,&nbsp;Leda R. Castilho ,&nbsp;Jerson Lima da Silva ,&nbsp;Liza F. Felicori","doi":"10.1016/j.molimm.2025.10.008","DOIUrl":"10.1016/j.molimm.2025.10.008","url":null,"abstract":"<div><div>Horse immunoglobulins have been utilized for over a century in serotherapy to treat venomous animal bites and various other conditions. However, molecular-level information about these immunoglobulins remains limited, particularly regarding immunoglobulin lambda light chains (Igλ), which constitute over 90 % of circulating antibodies. Despite the sequencing of the equine genome, the International ImMunoGeneTics information system (IMGT) has not yet annotated Igλ in its database, restricting the analysis of the horse antibody repertoire. In this study, we analyzed the equine Igλ repertoire and inferred the characteristics of the promoter regions and nearby co-stimulatory elements based on conserved human sequences. We find that some motifs from the promoter region of horse immunoglobulins showed a high rate of conservation between human and equine sequences, as an example of the octamer region. By mapping the V and J gene segment positions from EquCab2 to their corresponding positions in EquCab3, we constructed a library with new potential alleles. This impacted the annotation, since we identified the J gene segment J4S1^*01, which shares the same sequence as the J5 and J6S1 gene segments, account for over 50 % of the annotated J genes. Our analysis, which included a 2-fold increase in the number of clones compared to previous studies, revealed a restricted use of V gene segments, with approximately 70 % of the repertoire derived from just four gene segments within subgroup 8. This preference can be attributed to the presence of several co-stimulatory elements near the promoter region. Additionally, our analysis indicated that the CDR-L3 region predominantly displays lengths of 10–11 amino acids, with serine (Ser) being the most common amino acid. Beyond enhancing the annotation and characterization of the equine Igλ repertoire, this study also identified non-coding regions, particularly promoter regions containing a conserved octamer and a TATA-Box, and their co-stimulatory elements, such as pyrimidine-rich region, and E-box. The findings of this research contribute to a better understanding of equine Igλ composition, gene usage, and promoter characteristics, ultimately advancing future studies involving the use of equine antibodies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 1-11"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145384258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neohesperidin ameliorates airway remodeling through suppressed airway inflammation and oxidative stress in ovalbumin-sensitized mice","authors":"Shu-Chen Cheng ,&nbsp;Chian-Jiun Liou ,&nbsp;Ya-Ling Chen ,&nbsp;Li-Wen Fang ,&nbsp;Tse-Hung Huang ,&nbsp;Wen-Chung Huang","doi":"10.1016/j.molimm.2025.10.011","DOIUrl":"10.1016/j.molimm.2025.10.011","url":null,"abstract":"<div><div>Neohesperidin, a natural flavonoid found in citrus plants, has been reported to exhibit anti-inflammatory and antioxidant activities. In this study, we investigated its therapeutic potential in an ovalbumin (OVA)-induced murine model of allergic asthma. Female BALB/c mice were sensitized and challenged with OVA, followed by intraperitoneal administration of neohesperidin at doses of 10 or 20 mg/kg. The primary assessments included airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage fluid (BALF), lung histopathology, immunohistochemical analysis, and evaluation of oxidative stress biomarkers. In parallel, BEAS-2B human bronchial epithelial cells were stimulated with IL-4 and TNF-α to assess the anti-inflammatory and antioxidant effects of neohesperidin <em>in vitro</em>. Neohesperidin significantly attenuated several pathological features of asthma, including AHR, inflammatory cell infiltration, goblet cell hyperplasia, and collagen deposition. It not only suppressed Th2 cytokine levels and pro-inflammatory mediators in BALF, but also enhanced the activity of antioxidant enzymes in the lungs. Moreover, neohesperidin downregulated COX-2 expression and upregulated HO-1 in lung tissues. In BEAS-2B cells, it inhibited the release of inflammatory cytokines, reduced reactive oxygen species production, and decreased monocyte adhesion. Taken together, these findings suggest that neohesperidin possesses immunomodulatory and antioxidant properties that contribute to the attenuation of airway inflammation and remodeling in allergic asthma. These results indicate that neohesperidin is a promising natural compound with therapeutic potential for asthma treatment.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 27-37"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145384260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the role of nuclear factor erythroid 2–related factor 2 pathway on T cell & endothelial cell-based in vitro autoimmune disease model","authors":"Hatice İlke Özeken ,&nbsp;Derya Sağraç ,&nbsp;Oğuz Kaan Kırbaş ,&nbsp;Pakize Neslihan Taşlı ,&nbsp;Fikrettin Şahin","doi":"10.1016/j.molimm.2025.11.002","DOIUrl":"10.1016/j.molimm.2025.11.002","url":null,"abstract":"<div><div>Autoimmune disease is a complex condition where the immune system mistakenly attacks healthy tissues and affects millions around the world. Although there is no definitive cure or effective treatment, targeting the interaction between leukocytes and vascular endothelium presents a promising strategy for reducing excessive immune infiltration. Among strategies, combating oxidative stress and inflammation by activating antioxidant and anti-inflammatory genes is the best solution to decrease immune filtration. Nuclear-factor-erythroid 2-related factor-2 (NRF2) is a key player regulating oxidative stress and inflammation. This study investigates the anti-inflammatory impacts of the NRF2 pathway on the activated T cells that nonspecifically induce endothelial inflammation. To explore this, the NRF2 pathway in Human Umbilical Vein Endothelial Cells (HUVEC) was induced by using two approaches: NRF2 gene overexpression through the lentiviral systems (NRF2OE) and synthetic inducer, tert-butyl hydroquinone (TBHQ). These types of conditioned cells were co-cultured with activated Jurkat T cells to evaluate any regulatory effects of the NRF2 protein. Here, we observed that NRF2OE HUVEC cells induced a possible phenotypic shift from pro-inflammatory Th1 cells to anti-inflammatory Treg cells through upregulation of IL10 expression and downregulation of IL2 and IL2RA. This shift may demonstrate that NRF2 and its downstream pathway may help regulate immune responses by enhancing immune tolerance and reducing inflammation. Overall, these findings highlight the NRF2 pathway as a powerful modulator of endothelial inflammation and indicate its potential as a valuable therapeutic target for treating autoimmune diseases.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 111-120"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement factor D is a drug target for metabolic-associated fatty liver disease","authors":"Rong Guo ,&nbsp;Ziyun Li ,&nbsp;Jie Wu ,&nbsp;Zilin Zhang ,&nbsp;Junxiang Shu ,&nbsp;Xiaoxi Zhou ,&nbsp;Wenfang Zhou ,&nbsp;Yiming Chen ,&nbsp;Dongxia Guan ,&nbsp;Qian Wang ,&nbsp;Qiping Shi ,&nbsp;Hengwen Yang ,&nbsp;Guangqiang Li","doi":"10.1016/j.molimm.2025.11.006","DOIUrl":"10.1016/j.molimm.2025.11.006","url":null,"abstract":"<div><div>Metabolic dysfunction-associated fatty liver disease (MAFLD) is a globally prevalent disorder linked to metabolic syndrome, currently lacking approved therapies, and existing treatments offer only limited benefits. Complement factor D (CFD), a rate-limiting serine protease in the alternative complement pathway, has been suggested to be associated with metabolic diseases in previous studies. Its inhibitor, danicopan, is primarily used for paroxysmal nocturnal hemoglobinuria (PNH), but its role in metabolic liver diseases remains underexplored. Here, we assessed the role of CFD in MAFLD and danicopan therapy using HFD mice, patient sera, and hepatocytes via CRISPR knockout and pharmacological interventions. Key findings demonstrated significant upregulation of CFD in MAFLD mice livers and patient sera. Genetic CFD ablation attenuated hepatocyte lipid deposition. Danicopan reduced intracellular triglycerides/cholesterol, improved glucose tolerance, lowered ALT, and alleviated hepatic steatosis in obese mice without weight change. Mechanistically, danicopan suppressed NF-κB signaling, inhibiting lipid-related genes (CD36/FASN/ FATP2) and inflammatory mediators (MMP12/IL-6/TNF-α). These results establish CFD as a novel MAFLD mediator, validating FDA-approved danicopan's therapeutic efficacy and translational potential. This work provides critical evidence for targeting the CFD pathway in MAFLD management.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 192-200"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential impact of porcine reproductive and respiratory virus and swine Influenza A virus infections on respiratory Lymph Nodes B cells and macrophages","authors":"C. Hervet ,&nbsp;A. Perrin ,&nbsp;P. Renson ,&nbsp;C. Deblanc ,&nbsp;M. Muñoz ,&nbsp;F. Meurens ,&nbsp;J. Argilaguet ,&nbsp;G. Simon ,&nbsp;O. Bourry ,&nbsp;P. Maisonnasse ,&nbsp;N. Bertho","doi":"10.1016/j.molimm.2025.10.010","DOIUrl":"10.1016/j.molimm.2025.10.010","url":null,"abstract":"<div><div>Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) has a profound impact on the swine industry due to its ability to persist in infected animals. The PRRSV family exhibits considerable genetic variability, with PRRSV-1 and PRRSV-2 now classified as two distinct species (<em>Betaarterivirus suid</em> 1 and 2). Interestingly, both species – and their corresponding attenuated vaccine strains – can persist for months, in part by delaying the appearance of neutralizing antibodies. Leveraging recently developed tools for in-depth analysis of the previously poorly characterized porcine inverted lymph node (LN), we investigated early events in LN B cell maturation during PRRSV-1 infection and compared them to those induced by acute swine influenza A virus infection. We highlighted PRRSV-specific mechanisms, including PD-L1 upregulation in efferent macrophages, the presence of extrafollicular centrocytes, and the influx of inflammatory monocytes/macrophages. These findings are consistent with previous observations in PRRSV-2 infections and may therefore reflect conserved immune evasion mechanisms across PRRSV strains.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 98-110"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel single-chain antibody recognises complex glycan/alpha helix epitope in glycated haemoglobin using a subset of its complementarity determining regions","authors":"Lucia Gaetani ,&nbsp;Matthew Jenner ,&nbsp;James A. Schouten ,&nbsp;Paul Davis ,&nbsp;Richard Napier ,&nbsp;Ann M. Dixon","doi":"10.1016/j.molimm.2025.11.009","DOIUrl":"10.1016/j.molimm.2025.11.009","url":null,"abstract":"<div><div>Understanding the molecular interactions that govern antibody recognition of glycated epitopes is crucial for developing advanced diagnostics and therapeutics. This requires identification of the region of the antigen that is recognized (the epitope) and the regions of the antibody that bind the antigen (the paratope). Recently, we developed a single-chain variable fragment antibody (scFv) with high affinity and specificity for a complex, non-A1c epitope of haemoglobin that is both glycated and conformational. Here, we have used immunochemical and biophysical methods, including carbene footprinting mass spectrometry, to map the scFv’s epitope in human glycated haemoglobin. The epitope is composed of a glycation site at Lys-66 on the β globin chain and two α-helical regions spanning residues 9–17 and 67–72 that form a contiguous binding site on the protein’s surface. The identity of the paratope within the scFv was also determined, and we found that only a subset of the predicted complementarity determining regions (CDRs) participate in interactions with the antigen. A computational model of the scFv-HbA1c complex was created and used to indicate key residues in the CDRs and framework regions that mediate paratope-epitope interaction. This work advances our understanding of the molecular basis for high-affinity binding antibodies to complex glycated epitopes and provides a foundation upon which to develop innovative diagnostics that can detect multiple glycated species in parallel.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 168-178"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of YY1 with STING activation and the inflammatory response during early muscle injury repair","authors":"Xili Yan ,&nbsp;Zhongxing Hou ,&nbsp;Wenxin Li ,&nbsp;Shuang Miao ,&nbsp;Zejia Zhang ,&nbsp;Jie Luo ,&nbsp;Yinan Tao ,&nbsp;Qiang Li ,&nbsp;Jian Zhao ,&nbsp;Zhiliang Xu","doi":"10.1016/j.molimm.2025.11.011","DOIUrl":"10.1016/j.molimm.2025.11.011","url":null,"abstract":"<div><h3>Background</h3><div>Skeletal muscle injury is a common sports injury. Although the cGAS-STING signaling pathway is implicated in myoblast differentiation and muscle regeneration, its precise mechanisms remain unclear. Yin Yang 1 (YY1), a multifunctional transcriptional and chromatin regulator involved in various pathologies, also requires investigation for its specific role in regeneration.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate the association between YY1 and cGAS-STING pathway activation during early muscle regeneration, and explore its potential role in the inflammatory phase of myoblast differentiation.</div></div><div><h3>Methods</h3><div>A skeletal muscle injury model was established in C57BL/6 mice using 1.2 % barium chloride. H&amp;E staining evaluated muscle regeneration. Immunohistochemistry (IHC) quantified MyoG, YY1, H2Bub, and RNF20 expression. Immunofluorescence (IF) determined STING and YY1 expression. Western blotting measured cGAS, STING, YY1, caspase-3, IRF3, P-IRF3,P-TBK1, H2Bub and RNF20 protein levels. qPCR analyzed mRNA of inflammatory factors (IL-6, IL-17, IL-1β, TNF-α), myogenic regulators (MyoD, MyoG, Myf5), and signaling molecules (cGAS, STING, YY1, IRF3, caspase-3). Co-immunoprecipitation (Co-IP) assessed STING-YY1 interaction.</div></div><div><h3>Results</h3><div>Post-injury histology revealed significant pathology and inflammation. qPCR indicated upregulated mRNA levels of inflammatory factors and myogenic/signaling molecules at day 3, with partial recovery by day 7. Consistently, IHC (YY1, H2Bub, RNF20), IF (STING, YY1), and WB (cGAS, STING, YY1, caspase-3, IRF3, P-IRF3,P-TBK1, H2Bub and RNF20) all demonstrated elevated expression at day 3, declining by day 7. Co-IP confirmed a direct STING-YY1 interaction.</div></div><div><h3>Conclusion</h3><div>Our findings reveal a significant association between YY1 and cGAS-STING signaling activation, suggesting that this interplay contributes to the modulation of the inflammatory response during the early phase of skeletal muscle repair.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 142-153"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astragalus polysaccharide promotes CD8 + T cell activity by downregulating Tim-3 to potentiate antitumor immunity","authors":"Peijuan Liu ,&nbsp;Shuang Wang ,&nbsp;Yixiao Bin ,&nbsp;Zhiqian Xin ,&nbsp;Haijiao Yang ,&nbsp;Tianjiao Zhang ,&nbsp;Wangge Xie ,&nbsp;Ke Wang ,&nbsp;Wen Yin ,&nbsp;Hai Zhang","doi":"10.1016/j.molimm.2025.11.010","DOIUrl":"10.1016/j.molimm.2025.11.010","url":null,"abstract":"<div><div>It is well known that <em>Astragalus</em> polysaccharide (APS) exerts potent antitumor effects by enhancing T cell cytotoxicity via the PD-1/PD-L1 axis. However, whether APS can also modulate T cell activity via alternative checkpoint molecules remains unclear. Here, we addressed this question using complementary in vitro and in vivo approaches. In vitro, APS reduced the Tim-3 + cell population among human PBMCs. Further analysis revealed that APS specifically affected only the proportion of Tim-3 +CD8 + T cells. Along with the decreased proportion of Tim-3 + cells, CD8 + T cell immune activity was enhanced, as shown by increased expression of the early activation molecule CD69, increased secretion of GZMB, and enhanced capacity to kill human lung cancer cells. The results of transcriptome sequencing suggested that the APS-induced downregulation of Tim-3 might be related to the regulation of the transcription factor RORB. Experiments in an in vivo B16-F10 melanoma model revealed that APS enhanced T cell function by reducing the number of tumor-infiltrating Tim-3 + T cells, consequently suppressing tumor cell proliferation in mice. Collectively, our findings demonstrate that APS reduces the Tim-3 +CD8 + T cell population among PBMCs and enhances T cell cytotoxicity, providing a novel theoretical foundation for explaining the mechanism underlying APS immunomodulation.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"188 ","pages":"Pages 121-130"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}