Frontiers in Immunology最新文献

{"title":"Telitacicept as an alternative to non-steroidal immunosuppressive therapies in the treatment of myasthenia gravis: a study on clinical efficacy and steroid-sparing effect.","authors":"Zheyu Fang, Yuan Zhang, Yu Zhang, Qiaoyi Zhang, Xi Qu, Shengli Pan, Bingbing Wan, Shiyin Yang, Xu Zhang, Jia Li","doi":"10.3389/fimmu.2025.1549034","DOIUrl":"10.3389/fimmu.2025.1549034","url":null,"abstract":"<p><strong>Introduction: </strong>Myasthenia Gravis (MG) is an autoimmune disorder characterized by impaired neuromuscular junction (NMJ) transmission. Current treatments for MG include steroids and nonsteroidal immunosuppressive therapies (NSISTs). However, approximately 20% of patients show a poor response to these therapies, which are often associated with significant side effects. Telitacicept, a novel recombinant fusion protein targeting the BAFF/APRIL pathway, has shown promise in treating autoimmune diseases, including MG.</p><p><strong>Methods: </strong>This retrospective study compared the efficacy of telitacicept monotherapy (10 patients) to NSISTs (16 patients) and sequential therapy (6 patients) in managing Myasthenia Gravis (MG) at The First Affiliated Hospital of Wenzhou Medical University (July 2020-November 2024). The primary endpoint was the time to achieve minimal symptom expression (MSE), and secondary endpoint was the change in the mean daily prednisone dosage from baseline to month 4.</p><p><strong>Results: </strong>Among telitacicept-treated patients, 80% achieved MSE within 4 months, with a significant reduction in mean daily dose of prednisone (from 45.00 mg to 6.25 mg, <i>P</i> < 0.001). In contrast, only 12.5% of the NSISTs group achieved MSE, with no significant change in mean daily dose of prednisone (<i>P</i> = 0.091). The sequential therapy group (efgartigimod followed by telitacicept) maintained stable disease conditions.</p><p><strong>Conclusion: </strong>Telitacicept is effective in inducing MSE rapidly and offers a steroid-sparing effect, making it a promising alternative to traditional NSISTs with fewer side effects in MG patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1549034"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutations in ace2 gene modulate cytokine levels and alter immune responses in <i>Mycobacterium tuberculosis</i> and SARS-CoV-2 co-infection: a Cameroonian cohort.","authors":"Mary Ngongang Kameni, Eric Berenger Tchoupe, Severin Donald Kamdem, Nikhil Bhalla, Jean Paul Assam Assam, Arnaud Njuiget Tepa, Fuh Roger Neba, Ranjan Kumar Nanda, Anthony Afum-Adjei Awuah, John Humphrey Amuasi, Palmer Masumbe Netongo","doi":"10.3389/fimmu.2025.1533213","DOIUrl":"10.3389/fimmu.2025.1533213","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;SARS-CoV-2 and &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; (Mtb) share similarities in their modes of transmission, pathophysiological symptoms, and clinical manifestations. An imbalance in the immune response characterised by elevated levels of some inflammatory cytokines caused by tuberculosis (TB) and COVID-19 may increase the risk of developing a severe disease-like condition. It has been reported that TB increases the expression levels of Ace2 (angiotensin converting enzyme 2) and Tmprss2 (transmembrane protease serine 2) proteins, which are essential for COVID-19 pathogenesis. Single nucleotide polymorphisms (SNPs) variants of &lt;i&gt;ace2&lt;/i&gt; and &lt;i&gt;tmprss2&lt;/i&gt; genes can impact virus and host-cell interactions and alter immune responses by modulating cytokine production. This may modify the susceptibility and/or severity in COVID-19-infected people. The role of SNPs in &lt;i&gt;ace2&lt;/i&gt; and &lt;i&gt;tmprss2&lt;/i&gt; in relation to Mtb and SARS-CoV-2 co-infection is relatively underexplored.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;In this study, genotype frequency of 10 SNPs of &lt;i&gt;ace2&lt;/i&gt; and 03 SNPs of &lt;i&gt;tmprss2&lt;/i&gt; genes in a Cameroonian cohort consisting of COVID-19-positive (n = 31), TB-positive (n = 43), TB-COVID-19 co-infected (n = 21), and a control group (n = 24) were studied. The immune response was estimated by quantitating inflammatory cytokine levels alongside self-reported and clinically diagnosed symptoms. The relationship between specific genetic mutations in these ace2 gene SNPs and their impact on cytokine expression levels in Mtb and SARS-CoV-2 co-infected patients was investigated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified wild-type, heterozygous, and double-mutant genotypes in seven SNPs (rs2285666, rs6632677, rs4646116, rs4646140, rs147311723, rs2074192 and rs4646142) in &lt;i&gt;ace2&lt;/i&gt; gene, which showed significant variations in distribution across the study groups. Our most significant findings include the association of double mutant alleles (AA) of rs4646140 and rs2074192 in the &lt;i&gt;ace2&lt;/i&gt; gene with decreased IL-6 and IL-2 expression levels respectively in TB-COVID-19 participants. Also, the double mutant alleles (AA) of rs4646116 were responsible for increased expression level of IL-2 in TB-COVID-19 patients. Additionally, elevated serum levels of AST, urea, and D-dimer, as well as increased plasma concentrations of IL-10, IFN-γ, and TNF-α, have been associated with co-infections involving Mtb and SARS-CoV-2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;These biomarkers may reflect the complex interplay between the two pathogens and their impact on host immune responses and disease progression. This study highlights the critical role of genetic and immunological factors in shaping altered immune responses during co-infections involving Mtb and SARS-CoV-2. By elucidating these factors, the findings provide a foundation for a deeper understanding of host-pathogen interactions and their implications for disease progression and out","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1533213"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer analysis of co-inhibitory molecules revealing their potential prognostic and clinical values in immunotherapy.","authors":"Xiaoyu Ren, Anjie Guo, Jiahui Geng, Yuling Chen, Xue Wang, Lian Zhou, Lei Shi","doi":"10.3389/fimmu.2025.1544104","DOIUrl":"10.3389/fimmu.2025.1544104","url":null,"abstract":"<p><strong>Background: </strong>The widespread use of immune checkpoint inhibitors (anti-CTLA4 or PD-1) has opened a new chapter in tumor immunotherapy by providing long-term remission for patients. Unfortunately, however, these agents are not universally available and only a minority of patients respond to them. Therefore, there is an urgent need to develop novel therapeutic strategies targeting other co-inhibitory molecules. However, comprehensive information on the expression and prognostic value of co-inhibitory molecules, including co-inhibitory receptors and their ligands, in different cancers is not yet available.</p><p><strong>Methods: </strong>We investigated the expression, correlation, and prognostic value of co-inhibitory molecules in different cancer types based on TCGA, UCSC Xena, TIMER, CellMiner datasets. We also examined the associations between the expression of these molecules and the extent of immune cell infiltration. Besides, we conducted a more in-depth study of VISTA.</p><p><strong>Result: </strong>The results of differential expression analysis, correlation analysis, and drug sensitivity analysis suggest that CTLA4, PD-1, TIGIT, LAG3, TIM3, NRP1, VISTA, CD80, CD86, PD-L1, PD-L2, PVR, PVRL2, FGL1, LGALS9, HMGB1, SEMA4A, and VEGFA are associated with tumor prognosis and immune cell infiltration. Therefore, we believe that they are hopefully to serve as prognostic biomarkers for certain cancers. In addition, our analysis indicates that VISTA plays a complex role and its expression is related to TMB, MSI, cancer cell stemness, DNA/RNA methylation, and drug sensitivity.</p><p><strong>Conclusions: </strong>These co-inhibitory molecules have the potential to serve as prognostic biomarkers and therapeutic targets for a broad spectrum of cancers, given their strong associations with key clinical metrics. Furthermore, the analysis results indicate that VISTA may represent a promising target for cancer therapy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1544104"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoid receptor inhibits Th2 immune responses by down-regulating Pparg and Gata3 in schistosomiasis.","authors":"Tao Sun, Xiaojuan Bi, Ning Yang, Xue Zhang, Jin Chu, Liang Li, Hui Liu, Rui Tang, Renyong Lin","doi":"10.3389/fimmu.2025.1518586","DOIUrl":"10.3389/fimmu.2025.1518586","url":null,"abstract":"<p><strong>Introduction: </strong>The Th2 immune response plays a pivotal role in the pathogenesis of schistosomiasis, contributing to the formation of hepatic granulomas and fibrosis. While the glucocorticoid receptor (GR) is a ubiquitously expressed nuclear receptor that mediates anti-inflammatory effects, its impact on Th2 responses in schistosomiasis remains underexplored. Thus, this study aimed to investigate the potential impact of GR activation on the hepatic Th2 immune response in schistosomiasis using the synthetic glucocorticoid dexamethasone.</p><p><strong>Method: </strong><i>In vivo</i>, <i>Schistosoma japonicum</i>-infected mice were treated with dexamethasone, while in vitro studies were conducted on Th2 cells. Additionally, RNA sequencing and single-cell sequencing were integrated to identify key transcription factors influenced by GR activation during Th2 cell differentiation, with gene expression levels validated both in vivo and in vitro.</p><p><strong>Results: </strong><i>In vivo</i>, GR activation markedly reduced the size of <i>Schistosoma egg</i> granulomas and substantially repressed the transcription of key Th2-related cytokines, such as IL-4, IL-5, and IL-13. <i>In vitro</i>, GR activation inhibited the transcription of IL-4, IL-5, and IL-13, as well as the secretion of IL-4 in Th2 cells. An integrated analysis of RNA sequencing and single-cell sequencing revealed that GR activation downregulated the expression of two major transcription factors, Gata3 and Pparg, which were elevated in infected mouse livers and Th2 cells but decreased following dexamethasone treatment.</p><p><strong>Conclusion: </strong>GR activation may suppress the Th2 immune response triggered by egg antigens by downregulating the expression of the key transcription factors Gata3 and Pparg. While these findings provide insights into a potential complementary therapeutic strategy, further research is necessary to assess the feasibility and safety of targeting GR activation for the treatment of schistosomiasis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1518586"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pipelines for lymphocyte homeostasis maintenance during cancer immunotherapy.","authors":"Bensu Du, Jin Geng, Bin Wu, Houru Wang, Ru Luo, Hanmeng Liu, Rui Zhang, Fengping Shan, Lei Liu, Shuling Zhang","doi":"10.3389/fimmu.2025.1522417","DOIUrl":"10.3389/fimmu.2025.1522417","url":null,"abstract":"<p><p>In general, increasing lymphocyte entry into tumor microenvironment (TME) and limiting their efflux will have a positive effect on the efficacy of immunotherapy. Current studies suggest maintenance lymphocyte homeostasis during cancer immunotherapy through the two pipelines tumor-associated high endothelial venules and lymphatic vessels. Tumor-associated high endothelial venules (TA-HEVs) play a key role in cancer immunotherapy through facilitating lymphocyte trafficking to the tumor. While tumor-associated lymphatic vessels, in contrast, may promote the egress of lymphocytes and restrict their function. Therefore, the two traffic control points might be potential to maintain lymphocyte homeostasis in cancer during immunotherapy. Herein, we highlight the unexpected roles of lymphocyte circulation regulated by the two gateways for through reviewing the biological characters and functions of TA-HEVs and tumor-associated lymphatic vessels in the entry, positioning and exit of lymphocyte cells in TME during anti-tumor immunity.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1522417"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum miRNA-186-3P and miRNA-382-3P constitute a novel Diagnostic miRNA signature for palindromic rheumatism.","authors":"Fangfang Yuan, Zefu Weng, Qiong Yang, Jing Luo, Lina Ying, Haiyan Huang, Xin Zhang, Yahui Chen, Jixia Lin, Junhong He","doi":"10.3389/fimmu.2025.1569846","DOIUrl":"10.3389/fimmu.2025.1569846","url":null,"abstract":"<p><strong>Background: </strong>Palindromic rheumatism (PR) is a unique disease characterized by the intermittent inflammation of different joints that may progress to a variety of immune-related diseases. Unclear diagnostic criteria have limited the research on its pathogenesis and treatment options. Recently, microRNAs (miRNAs) have been used in the diagnosis of various diseases; however, the role of miRNAs in PR diagnosis remains unexplored. Using next-generation high-throughput sequencing (NGS), this study aimed to screen miRNAs specifically expressed in the serum of patients with PR to construct a miRNA signature and verify its diagnostic efficacy.</p><p><strong>Methods: </strong>Patients with PR (N=4), patients with rheumatoid arthritis (RA; N=3), and healthy individuals (Con; N=3) were included in an exploration cohort. Differentially expressed miRNAs were screened using NGS to construct a miRNA signature, and bioinformatics tools were used to perform target gene enrichment analysis of the top 25 differentially expressed miRNAs, both upregulated and downregulated. RT-qPCR was used to verify the differential expression of the miRNA signature in three validation cohorts of patients with PR (N=27) and RA (N=30), and healthy individuals (N=31). The efficiency of the miRNA signature was evaluated using receiver operator characteristic (ROC) curves, an analytical method that assesses diagnostic accuracy.</p><p><strong>Results: </strong>A total of 130 miRNAs were differentially expressed in the PR exploration cohort, including 35 upregulated and 95 downregulated compared to levels in the RA and healthy cohorts. miRNA-186-3p showed the largest upregulated difference and miRNA-382-3p the largest downregulated difference; these were selected to construct the miRNA signature. In the ROC curve of the validation cohort, the PR miRNA signature produced an area under the ROC curve (AUC) of 0.980 (95% CI 0.942-1.000) when distinguishing from healthy individuals and of 0.906 (95% CI 0.830-0.983) when distinguishing from RA patients. However, miRNA-186-3p and miRNA-382-3p levels were not associated with disease activity in patients with PR.</p><p><strong>Conclusion: </strong>A miRNA signature comprising miRNA-186-3p and miRNA-382-3p can effectively diagnose and differentiate PR from RA. This study provides a basis for the creation of a clinical miRNA signature for the diagnosis of PR.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1569846"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research trajectory and future trends in curcumin related to immunity: a bibliometric analysis of publications from last two decades.","authors":"Qing Hong, Wei Lyu, Chaowei Zhang, Weiyi Yao, Yuxuan Han, Na Chen","doi":"10.3389/fimmu.2025.1559670","DOIUrl":"10.3389/fimmu.2025.1559670","url":null,"abstract":"<p><p>Curcumin has a clear immunopharmacological effect and plays an important role as an immune agent in various immune diseases and tumor immunotherapy. To comprehensively and scientifically clarify and reflect the development process, current status, and research trends of curcumin in the field of immune regulation, and to provide reliable insights for discipline development strategies and future research expansion, this study systematically analyzes 3939 valid articles related to curcumin and immunity published between 2004 and 2024 from the Web of Science database. Using Citespace and R-bibliometrix software for bibliometric analysis, we create visual knowledge maps from multiple dimensions including overall publication output, influential research entities, highly cited papers, research topics and hotspots. The results indicate that the overall number of publications and citations is currently in a rapid development phase. China occupies a core position in this research field but has low collaboration intensity. The Egyptian Knowledge Bank (EKB) is the institution with the highest publication volume. Moreover, cluster analysis reveals that research hotspots are gradually shifting from fundamental pathology to topics involving broad social and environmental influences. The top five keywords with the most explosive citations-curcumin, inflammation, apoptosis, oxidative stress, and cancer-represent the most focused and influential research topics. Currently, curcumin immunology has developed a diversified research perspective, accumulating significant research in the areas of active substance basis, pharmacological activity, anti-inflammatory, and anti-cancer studies. The thematic evolution trends and keywords related to curcumin's immunological mechanisms summarized in this article provide insights and guidance for future research directions.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1559670"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of KDM5D as a novel biomarker for traumatic brain injury identified through bioinformatics analysis.","authors":"Dengfeng Ding, Mengzhe Yang, Xinou Zheng, Ming Zhao","doi":"10.3389/fimmu.2025.1538561","DOIUrl":"10.3389/fimmu.2025.1538561","url":null,"abstract":"<p><strong>Background and aim: </strong>Traumatic brain injury (TBI) poses a significant burden on the global economy due to its poor treatment and prognosis. Current TBI markers do not comprehensively reflect the disease status. Therefore, identifying more meaningful biomarkers is beneficial for improving the prognosis and clinical treatment of TBI patients.</p><p><strong>Methods: </strong>The gene expression profile of TBI was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were subjected to enrichment analysis, and key potential genes were identified through the protein-protein interaction network and cytoHubba modules. ROC curves were used to construct diagnostic models for hub genes. Immunofluorescence experiments were conducted to detect the expression of candidate biomarkers in TBI rat models. Finally, we investigated the expression of TBI biomarkers in normal human organs and pan-cancer tumor tissues, and evaluated their correlation with immune infiltration in different tumors.</p><p><strong>Results: </strong>A total of 44 DEGs were identified across four brain regions of TBI patients. Enrichment analysis revealed that these genes were primarily involved in intracellular and cell signal transduction pathways. Furthermore, three hub genes- RPS4Y1, KDM5D and NLGN4Y-were identified through different module analysis. The ROC curve diagnostic model also confirmed that these genes also have high diagnostic value in serum. Subsequently, the presence of Kdm5d was detected in the brain tissue of TBI rats through immunofluorescence experiments. Compared to normal rats, Kdm5d expression increased in the cortical area of ​​TBI rats, with no significant change in the hippocampus area, aligning with observations in TBI patients. Immune infiltration analysis demonstrated changes in immune cell subsets in HIP and PCx, revealing that plasma cells and CD8 T cells were lowly expressed in TBI (HIP) and while neutrophils was under-expressed in TBI (PCx). Pan-cancer analysis indicated that KDM5D was significantly up-regulated in 23 cancers, down-regulated in 3 cancers, and significantly associated with immune infiltration in 10 cancers.</p><p><strong>Conclusion: </strong>Based on the results of bioinformatics analysis and animal experiments, KDM5D serves as a potential biomarker for the diagnosis and prognosis of TBI. Additionally, research on KDM5D may develop into new serum markers, providing new indicators for further clinical liquid biopsy and aiding in the prevention of both TBI and tumors to a certain extent.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1538561"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dynamics at the intersection of macrophage polarization and metabolism.","authors":"Pan Li, Zhengbo Fan, Yanlan Huang, Liang Luo, Xiaoyan Wu","doi":"10.3389/fimmu.2025.1520814","DOIUrl":"10.3389/fimmu.2025.1520814","url":null,"abstract":"<p><p>Macrophages are vital sentinels in innate immunity, and their functions cannot be performed without internal metabolic reprogramming. Mitochondrial dynamics, especially mitochondrial fusion and fission, contributes to the maintenance of mitochondrial homeostasis. The link between mitochondrial dynamics and macrophages in the past has focused on the immune function of macrophages. We innovatively summarize and propose a link between mitochondrial dynamics and macrophage metabolism. Among them, fusion-related FAM73b, MTCH2, SLP-2 (Stomatin-like protein 2), and mtSIRT, and fission-related Fis1 and MTP18 may be the link between mitochondrial dynamics and macrophage metabolism association. Furthermore, post-translational modifications (PTMs) of mtSIRT play prominent roles in mitochondrial dynamics-macrophage metabolism connection, such as deacetylates and hypersuccinylation. MicroRNAs such as miR-150, miR-15b, and miR-125b are also possible entry points. The metabolic reprogramming of macrophages through the regulation of mitochondrial dynamics helps improve their adaptability and resistance to adverse environments and provides therapeutic possibilities for various diseases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1520814"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential target within the tumor microenvironment - MT1-MMP.","authors":"Jinlong Liu, Yijing Li, Xueqi Lian, Chenglin Zhang, Jianing Feng, Hongfei Tao, Zhimin Wang","doi":"10.3389/fimmu.2025.1517519","DOIUrl":"10.3389/fimmu.2025.1517519","url":null,"abstract":"<p><p>Matrix metalloproteinases are integral to the modification of the tumor microenvironment and facilitate tumor progression by degrading the extracellular matrix, releasing cytokines, and influencing the recruitment of immune cells. Among the matrix metalloproteinases, membrane-type matrix metalloproteinase 1 (MT1-MMP/MMP14) is the first identified membrane-type MMP and acts as an essential proteolytic enzyme that enables tumor infiltration and metastatic progression. Given the pivotal role of MT1-MMP in tumor progression and the correlation between its overexpression in tumors and unfavorable prognoses across multiple cancer types, a comprehensive understanding of the potential functional mechanisms of MT1-MMP is essential. This knowledge will aid in the advancement of diverse anti-tumor therapies aimed at targeting MT1-MMP. Although contemporary research has highlighted the considerable potential of MT1-MMP in targeted cancer therapy, studies pertaining to its application in cell therapy remain relatively limited. In this review, we delineate the structural characteristics and regulatory mechanisms of MT1-MMP expression, as well as its biological significance in tumorigenesis. Finally, we discussed the current status and prospects of anti-tumor therapies targeting MT1-MMP.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1517519"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}