Molecular immunology最新文献_第5页

Neferine reduces synovial inflammation and cardiac complications in a collagen-induced arthritis mouse model via inhibiting NF-κB/NLRP3 inflammasome axis 在胶原诱导的关节炎小鼠模型中，莲子碱通过抑制NF-κB/NLRP3炎症小体轴减少滑膜炎症和心脏并发症

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-04-21 DOI: 10.1016/j.molimm.2025.04.001

Jingjing Cao , Huaxing Zhang , Yanhui Ni , Xiaoran Ning

{"title":"Neferine reduces synovial inflammation and cardiac complications in a collagen-induced arthritis mouse model via inhibiting NF-κB/NLRP3 inflammasome axis","authors":"Jingjing Cao , Huaxing Zhang , Yanhui Ni , Xiaoran Ning","doi":"10.1016/j.molimm.2025.04.001","DOIUrl":"10.1016/j.molimm.2025.04.001","url":null,"abstract":"<div><div>For the treatment of rheumatoid arthritis (RA), there are limited options for drugs with fewer side effects. Neferine possesses anti-inflammatory, anti-fibrotic, and cardioprotective properties, but its effectiveness in the treatment of RA remains unclear. Our study aimed to explore the impact of neferine administration on ankle joint inflammation and cardiac complications of collagen-induced arthritis (CIA) mice. The CIA model was introduced in male DBA/1 mice via subcutaneous injection of Type II collagen (CII) into the tail. We found that neferine alleviated ankle joint inflammation, cartilage erosion, and bone destruction, as well as reduced the levels of IL-6, TNF-α, IL-1β, and IL-18 in the serum of CIA mice. Furthermore, neferine reduced the expression of synovial damage markers (RANKL, MMP-3, and MMP-13) in the ankle joints of CIA mice. Mechanistically, neferine lowered the levels of NF-κB pathway-related molecules such as p-IκBα, p-p65, and nuclear p65 in the synovial tissue of CIA mice. Simultaneously, neferine reversed the upregulation of NLRP3, ASC, and cleaved-caspase-1 levels in the synovial tissue of CIA mice. Additionally, our results showed that neferine reduced the contents of myocardial injury markers (cTnI, CK-MB, and LDH), alleviated myocardial fibrosis, decreased expression of α-SMA and Collagen I, as well as mitigated the activation of fibrosis-related TGF-β/Smad signaling. In summary, our study demonstrates that neferine attenuates chondral and synovial inflammation in a CIA mouse model by inhibiting the activation of the NF-κB/NLRP3 inflammasome, and neferine has a protective effect on the hearts of CIA mice.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 117-125"},"PeriodicalIF":3.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855069","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}

引用次数: 0

miR-23a-mediated TRF2 repression in CD4 T cells from PLWH miR-23a 在白血病患者 CD4 T 细胞中介导的 TRF2 抑制作用

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-04-19 DOI: 10.1016/j.molimm.2025.04.003

Lam N.T. Nguyen , Juan Zhao , Jaeden S. Pyburn , Ling Wang , Madison Schank , Puja Banik , Addison C. Hill , Xiao Y. Wu , Yi Zhang , Shunbin Ning , Mohamed El Gazzar , Jonathan P. Moorman , Zhi Q. Yao

{"title":"miR-23a-mediated TRF2 repression in CD4 T cells from PLWH","authors":"Lam N.T. Nguyen , Juan Zhao , Jaeden S. Pyburn , Ling Wang , Madison Schank , Puja Banik , Addison C. Hill , Xiao Y. Wu , Yi Zhang , Shunbin Ning , Mohamed El Gazzar , Jonathan P. Moorman , Zhi Q. Yao","doi":"10.1016/j.molimm.2025.04.003","DOIUrl":"10.1016/j.molimm.2025.04.003","url":null,"abstract":"<div><div>CD4 T cells in people living with HIV (PLWH) on antiretroviral therapy (ART) often exhibit an inflammaging phenotype, characterized by persistent inflammation, immune activation, exhaustion, senescence, and apoptosis. We have previously demonstrated that inhibition of telomeric repeat factor 2 (TRF2) protein causes accelerated telomere erosion and premature CD4 T cell aging in PLWH. In this study, we further investigated how TRF2 protein is inhibited in CD4 T cells from PLWH, focusing on the miRNA-mediated mechanism. We found that miR-23a is significantly increased, whereas TRF2 protein is repressed, in CD4 T cells from PLWH compared to healthy subjects (HS). Bioinformatics analysis revealed that the TRF2 3’UTR is a potential target of miR-23a. Co-transfection of miR-23a with a luciferase construct containing TRF2 3’UTR into HEK293T cells revealed that miR-23a suppresses TRF2 protein translation. Notably, T cell receptor (TCR) activation in CD4 T cells from both PLWH and HS increased miR-23a and decreased TRF2 protein expression. Furthermore, increasing miR-23a in CD4 T cells from HS led to a decrease in TRF2 protein level and an increase in cellular apoptosis - a phenotype similar to what we observed in PLWH. Moreover, the knockdown of miR-23a in CD4 T cells from PLWH increased TRF2, but not TRF1, protein levels. These results suggest that miR-23a negatively regulates TRF2 protein expression in CD4 T cells; thus, targeting miR-23a may increase TRF2 protein level, and thereby protect telomere integrity and restore CD4 T cell functions in PLWH.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 107-116"},"PeriodicalIF":3.2,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847910","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}

引用次数: 0

Steap3 is a key node in regulating the phagosome escape of Listeria monocytogenes Steap3是调控单核增生李斯特菌吞噬体逃逸的关键节点

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-04-18 DOI: 10.1016/j.molimm.2025.04.006

Zhangfu Li , Yan Shao , Xiao Liu , Xiaoyuan Wan , Pei Xiong , Liting Wang , Jiangbei Yuan

{"title":"Steap3 is a key node in regulating the phagosome escape of Listeria monocytogenes","authors":"Zhangfu Li , Yan Shao , Xiao Liu , Xiaoyuan Wan , Pei Xiong , Liting Wang , Jiangbei Yuan","doi":"10.1016/j.molimm.2025.04.006","DOIUrl":"10.1016/j.molimm.2025.04.006","url":null,"abstract":"<div><div><em>Listeria monocytogenes</em>, a foodborne pathogen, poses a significant threat to human health due to its high mortality rate and increasing antibiotic resistance. This study investigates the role of Steap3 in regulating the early phagosomal escape of <em>Listeria monocytogenes</em>. We found that Steap3 expression is downregulated in dendritic and intestinal epithelial cells following infection, and its deficiency exacerbates bacterial proliferation both in vitro and in vivo. Mechanistically, Steap3 interacts with Gm2a and Sting to inhibit <em>Listeria monocytogenes</em> infection. Our results highlight Steap3 as a key regulator in dendritic and intestinal epithelial cells’ defense against <em>Listeria monocytogenes</em> infection, suggesting the Steap3-STING/Gm2a axis is a potential therapeutic target for listeriosis. This study provides valuable insights into the molecular mechanisms underlying <em>Listeria monocytogenes</em> pathogenesis and host immune response, offering new directions for developing anti-<em>Listeria monocytogenes</em> therapies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 96-106"},"PeriodicalIF":3.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842912","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}

引用次数: 0

Methotrexate loaded extracellular vesicles attenuate periodontitis by suppressing ACSL1 and promoting anti-inflammatory macrophage 甲氨蝶呤负载细胞外囊泡通过抑制ACSL1和促进抗炎巨噬细胞减轻牙周炎

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-04-16 DOI: 10.1016/j.molimm.2025.04.005

Zhi Liu , Jianhua Yang , Guodong Tan , Yuanyuan Shi , Dihao Tao , Wenzhe Wang , Bei Li , Fang Jin , Xiaoning He

{"title":"Methotrexate loaded extracellular vesicles attenuate periodontitis by suppressing ACSL1 and promoting anti-inflammatory macrophage","authors":"Zhi Liu , Jianhua Yang , Guodong Tan , Yuanyuan Shi , Dihao Tao , Wenzhe Wang , Bei Li , Fang Jin , Xiaoning He","doi":"10.1016/j.molimm.2025.04.005","DOIUrl":"10.1016/j.molimm.2025.04.005","url":null,"abstract":"<div><div>Macrophages are crucial immune cells in periodontal tissues, which play key roles in both the destruction and repair of associated with periodontitis. Targeted modulation of macrophage function has emerged as a potentially effective approach to influence periodontitis progression. This study investigates the effects of methotrexate-loaded extracellular vesicles (MTX-EVs) on inflammatory macrophage polarization both in vivo and in vitro. In a murine periodontitis model, MTX-EVs inhibited alveolar bone resorption, suppressed pro-inflammatory macrophage activation, and promoted anti-inflammatory macrophages. Mechanistically, MTX-EVs reduced acyl-CoA synthetase-1 (ACSL1) expression, which was elevated during inflammation. Inhibition of ACSL1 with triacsin-C in macrophages suppressed the inflammatory phenotype through the promotion of the oxidative phosphorylation (OXPHOS). In contrast, MTX-EVs counteracted the effects of ACSL1 overexpression on macrophage polarization and metabolism. Our findings suggest that targeting ACSL1 via MTX-EVs represents a therapeutic strategy for modulating macrophage polarization and improving periodontitis treatment outcomes.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 83-95"},"PeriodicalIF":3.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834255","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}

引用次数: 0

HLA Class I and II allelic diversity among Ecuadorian transplant candidates: A comprehensive retrospective analysis 厄瓜多尔移植候选者HLA I类和II类等位基因多样性：一项全面的回顾性分析

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-04-15 DOI: 10.1016/j.molimm.2025.03.019

Erick Velasteguí , María Esther Castillo , Felipe Ortiz , Sofía Espín , Eduardo Espinel , Luis Alberto Loyola , David Báez-Cevallos , Nikolaos C. Kyriakidis , Daniel Romero-Alvarez , Isabel Baroja , Carlos Bastidas-Caldes

{"title":"HLA Class I and II allelic diversity among Ecuadorian transplant candidates: A comprehensive retrospective analysis","authors":"Erick Velasteguí , María Esther Castillo , Felipe Ortiz , Sofía Espín , Eduardo Espinel , Luis Alberto Loyola , David Báez-Cevallos , Nikolaos C. Kyriakidis , Daniel Romero-Alvarez , Isabel Baroja , Carlos Bastidas-Caldes","doi":"10.1016/j.molimm.2025.03.019","DOIUrl":"10.1016/j.molimm.2025.03.019","url":null,"abstract":"<div><div>The Major Histocompatibility Complex (MHC) comprises over 220 genes encoding proteins that are vital for the functioning of the immune system. These genes are divided into three classes: HLA class I, II, and III. The polymorphism of MHC genes serves to enhance the immune response by increasing the diversity of antigen presentation. In Ecuador, a country with a diverse population comprising numerous ethnic groups, it is crucial to comprehend the distribution of HLA alleles in order to facilitate several health approaches such as personalized medicine and organ transplantation. The present study employed data from Ecuador's National Institute of Organ, Tissue, and Cell Donation and Transplantation (INDOT) from 2017 to 2022. The data were analyzed to determine the distribution of HLA class I (HLA-A, HLA-B, HLA-C) and class II (HLA-DRB1, DRB3, DRB4, DQB1) alleles. A total of 1530 HLA alleles were identified among the 2352 patients included in the study. The highest variability was observed in Class I alleles, with HLA-A02 (32 %) and HLA-B35 (21 %) being the most common. In the case of class II, the most prevalent alleles were DRB104 and DQB103, with frequencies of 25.1 % and 48 %, respectively. It is notable that significant regional variations in allele frequencies were observed across Ecuador. The findings of this comprehensive study provide valuable insights into Ecuador's HLA allele distribution, contributing to genetic research, personalized medicine, and organ transplant matching. However, the results also highlight the need for further studies to better understand genetic diversity and improve public health strategies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 76-82"},"PeriodicalIF":3.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830355","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}

引用次数: 0

LncRNA XIST inhibits mitophagy and increases mitochondrial dysfunction by promoting BNIP3 promoter methylation to facilitate the progression of KBD LncRNA XIST通过促进BNIP3启动子甲基化，抑制线粒体自噬，增加线粒体功能障碍，促进大骨节病的进展

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-04-03 DOI: 10.1016/j.molimm.2025.03.016

Ruoxi Liu , Yi Xiao , Sihua Huang , Hao Wu , Jun Dong , Sixiang Zeng , Yongwei Li , Jintao Ye , Wei Wu , Mengxin Wang , Sanpeng Zhang , Zhaoxing Lin , Huanjin Song

{"title":"LncRNA XIST inhibits mitophagy and increases mitochondrial dysfunction by promoting BNIP3 promoter methylation to facilitate the progression of KBD","authors":"Ruoxi Liu , Yi Xiao , Sihua Huang , Hao Wu , Jun Dong , Sixiang Zeng , Yongwei Li , Jintao Ye , Wei Wu , Mengxin Wang , Sanpeng Zhang , Zhaoxing Lin , Huanjin Song","doi":"10.1016/j.molimm.2025.03.016","DOIUrl":"10.1016/j.molimm.2025.03.016","url":null,"abstract":"<div><div>The primary mechanisms underlying cartilage destruction in Kashin-Beck disease (KBD) involve excessive chondrocyte death and extracellular matrix (ECM) degradation. While long non-coding RNA XIST (lncRNA XIST) has been implicated in promoting chondrocyte injury in osteoarthritis (OA), its role in KBD-related chondrocyte injury remains poorly understood. In this study, joint tissues were collected from four healthy and four KBD-affected children, as well as five healthy and five KBD-affected adults, to assess the expression of lncRNA XIST. The results revealed a significant upregulation of lncRNA XIST in the cartilage tissues of KBD patients. To model KBD-induced chondrocyte damage in vitro, hypertrophic ATDC5 cells were exposed to 10 ng/ml T-2 toxin for 24 hours, which resulted in increased lncRNA XIST expression. Silencing lncRNA XIST was found to mitigate T-2 toxin-induced ECM degradation and chondrocyte apoptosis by alleviating defects in mitochondrial autophagy and dysfunction. Mechanistically, lncRNA XIST promoted the methylation of the BNIP3 promoter by recruiting DNA methyltransferases (DNMTs) to the BNIP3 promoter region, thereby suppressing BNIP3-mediated mitophagy and exacerbating mitochondrial dysfunction. To establish a KBD rat model, rats were fed a low-selenium diet supplemented with T-2 toxin for four weeks. Knockdown of lncRNA XIST in these rats attenuated articular cartilage damage and apoptosis, while enhancing collagen II expression. In conclusion, lncRNA XIST accelerates KBD progression by inhibiting mitophagy and promoting mitochondrial dysfunction through increased BNIP3 promoter methylation.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 62-75"},"PeriodicalIF":3.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759474","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}

引用次数: 0

MicroRNA-770 promotes polarization of macrophages and hemorrhoids by suppressing RYBP expression and monoubiquitination of histone H2A on Lys119 modification MicroRNA-770通过抑制RYBP的表达和Lys119修饰组蛋白H2A的单泛素化，促进巨噬细胞和痔疮的极化

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-04-01 DOI: 10.1016/j.molimm.2025.03.017

Haikun Zhou , Te Liu , Shenglan Zhong , Wei Yang

{"title":"MicroRNA-770 promotes polarization of macrophages and hemorrhoids by suppressing RYBP expression and monoubiquitination of histone H2A on Lys119 modification","authors":"Haikun Zhou , Te Liu , Shenglan Zhong , Wei Yang","doi":"10.1016/j.molimm.2025.03.017","DOIUrl":"10.1016/j.molimm.2025.03.017","url":null,"abstract":"<div><div>Hemorrhoid disease (HD) is a common proctological condition whose onset is associated with an abnormal inflammatory microenvironment; however, the underlying mechanisms remain unclear. In this study, pathological examination revealed a significant increase in MΦ1 macrophages in the hemorrhoidal tissue of patients with HD, along with elevated levels of inflammatory factors. qPCR results demonstrated that the expression of several members of the DLK1-DIO3 microRNA cluster, particularly miR-770, was significantly higher in the hemorrhoid tissue of patients with HD than in that of the control group. Luciferase reporter assays confirmed that RYBP is a target gene negatively regulated by miR-770. Additionally, qPCR and western blot analyses indicated that overexpression of miR-770 significantly downregulated the expression of PRC1 family genes and RYBP in THP-1 cells, while concurrently upregulating the expression of inflammatory factors such as NFKB, IL1b, IL4, TNF, and IFNG. The overexpression of miR-770 significantly induced the polarization of THP-1 cells toward MΦ1. Mechanistic studies using ChIP-seq revealed that miR-770 overexpression significantly reduced the number of gene promoters in MΦ1 cells that bind to histone H2AK119-Ub sites. Furthermore, the number of enriched DNA fragments from genes that bind to the + 1 transcription start site of histone H2AK119-Ub, such as NFKB1, IL1B, and TNF, was significantly lower than that observed in the control group. Therefore, we confirmed that miR-770, a genomic imprinted member of the DLK1-DIO3 region, negatively regulated the expression of the PRC1 family member RYBP, reduced the level of ubiquitination modification at histone H2AK119-Ub, and promoted the transcriptional activation of pro-inflammatory genes. This ultimately leads to MΦ1 polarization and the release of inflammatory factors, elucidating the epigenetic mechanisms underlying the occurrence of hemorrhoids.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 41-53"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748166","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}

引用次数: 0

NK cellular derived nanovesicles in tumor immunity NK细胞源性纳米囊泡在肿瘤免疫中的作用

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-04-01 DOI: 10.1016/j.molimm.2025.03.018

Dingru Li , Yixin Shi , Sifei Yu , Beiying Zhang , Ziyi Huang , Fei Ling , Xiaofan Mao , Yuhua Deng , Mengyun Cai , Wei Luo

{"title":"NK cellular derived nanovesicles in tumor immunity","authors":"Dingru Li , Yixin Shi , Sifei Yu , Beiying Zhang , Ziyi Huang , Fei Ling , Xiaofan Mao , Yuhua Deng , Mengyun Cai , Wei Luo","doi":"10.1016/j.molimm.2025.03.018","DOIUrl":"10.1016/j.molimm.2025.03.018","url":null,"abstract":"<div><div>Natural Killer (NK) cells are a vital element of the innate immune system, and NK cell-based therapies have demonstrated efficacy against various malignancies. However, targeting solid tumors has been challenging due to the low infiltration of NK cells into tumors and the effective evasion strategies employed by tumors. Recent studies have shown that NK cell derived nanovesicles (NK-NV) can not only replicate the functions of NK cells but also offer more advantages in clinical applications. They are capable of transporting various cellular components such as proteins, nucleic acids, and lipids across distances, thereby facilitating intercellular communication among various cells within the tumor microenvironment (TME). With the progress in nanomedical technology, these vesicles can be engineered to carry a range of functional elements and therapeutic agents to enhance their antitumoral capabilities. In this review, we summarize the current available literature on NK-NVs, discuss their potential biological functions and the role of non-coding RNAs (ncRNAs), and explore their application in the treatment of solid tumors.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 54-61"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-tumor effectiveness of a novel bispecific antibody that blocks both PD-L1 and LAG-3 阻断PD-L1和LAG-3的新型双特异性抗体的抗肿瘤效果

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-03-31 DOI: 10.1016/j.molimm.2025.03.015

Chenxing Zhang , Jiaxin Liu , Minglv Sun , Tiejun Gu , Xiangyu Meng , Shidong Zhu , Youfeng Zhang , Linlin Wang , Yan Chen , Daguang Zhang , Yongge Wu

{"title":"Anti-tumor effectiveness of a novel bispecific antibody that blocks both PD-L1 and LAG-3","authors":"Chenxing Zhang , Jiaxin Liu , Minglv Sun , Tiejun Gu , Xiangyu Meng , Shidong Zhu , Youfeng Zhang , Linlin Wang , Yan Chen , Daguang Zhang , Yongge Wu","doi":"10.1016/j.molimm.2025.03.015","DOIUrl":"10.1016/j.molimm.2025.03.015","url":null,"abstract":"<div><div>Over the past few years, substantial progress with promising outcomes were achieved for the use of antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in immunotherapy. However, several issues still limit their effectiveness for anti-cancer therapy. Therefore, we designed a bispecific antibody (referred to as Ba-PL) against PD-L1 and T cell immune checkpoint lymphocyte activation gene-3 (LAG-3), in an attempt to block both targets to further improve immune efficacy against solid tumors. A bispecific T cell engager structure was used to connect the variable regions of the PD-L1 and LAG-3 antibodies in series. The antibody was prepared using a prokaryotic expression system, and its molecular and cellular-level affinity was assessed in vitro. Furthermore, we preliminarily evaluated its anti-tumor effects in mice. Collectively, the antibody prepared using the prokaryotic expression system had preferable tumor cell-targeting ability and blocked the interaction of PD-1 and LAG-3 with their ligands. Further, the results of the animal experiments demonstrated that the Ba-PL exerted a better anti-tumor effect in 4T1 and H22 tumor-bearing mice. Overall, our study suggests that this strategy has therapeutic potential for liver hepatocellular and breast invasive carcinoma.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 30-40"},"PeriodicalIF":3.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739896","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}

引用次数: 0

Marvelon suppresses MC38 tumor growth and promotes anti-tumor immunity Marvelon抑制MC38肿瘤生长，促进抗肿瘤免疫

IF 3.2 3区医学

Molecular immunology Pub Date : 2025-03-29 DOI: 10.1016/j.molimm.2025.03.011

Fandi Kong , Yongyan Chen , Dantong Liu, Hongying Gao, Qiaoru Yi, Mengjuan Zhang, Dan Li

{"title":"Marvelon suppresses MC38 tumor growth and promotes anti-tumor immunity","authors":"Fandi Kong , Yongyan Chen , Dantong Liu, Hongying Gao, Qiaoru Yi, Mengjuan Zhang, Dan Li","doi":"10.1016/j.molimm.2025.03.011","DOIUrl":"10.1016/j.molimm.2025.03.011","url":null,"abstract":"<div><div>Colorectal cancer is a prevalent and deadly malignancy globally, posing an important challenge due to its heterogeneity and treatment resistance. Although oral contraceptives have been shown to reduce the incidence of colorectal cancer, their impact on the anti-tumor effect of CD8<sup>+</sup> T cells remains unclear. Here we show that the contraceptive Marvelon plays an important role in anti-MC38 tumor immunity. The contraceptive Marvelon significantly inhibits MC38 tumor growth in vivo. Marvelon treatment promotes IFN-γ expression in CD8<sup>+</sup> tumor infiltrating lymphocytes, but shows dispensable impact on their exhausted profile. By further investigating the effects of Marvelon’s primary components, Ethinylestradiol and Desogestrel, we reveal that Ethinylestradiol enhances IFN-γ production in Type 1 Cytotoxic T (Tc1) cells and significantly inhibits the viability of MC38 tumor cells, whereas Desogestrel exhibits minimal effects. This study not only redefines the role of oral contraceptives but also provides valuable insights for the development of novel immunotherapeutic strategies.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"182 ","pages":"Pages 20-29"},"PeriodicalIF":3.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725157","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}

引用次数: 0