Frontiers in Immunology最新文献

{"title":"Contribution of cuproptosis and immune-related genes to idiopathic pulmonary fibrosis disease.","authors":"Chengji Jin, Jia Li, Qiaoyu Li, Lipeng Zhang, Shaomao Zheng, Qiong Feng, Yongjie Li, Yu Zheng, Qiuli Nie, Jin Liang, Jing Wang","doi":"10.3389/fimmu.2025.1458341","DOIUrl":"10.3389/fimmu.2025.1458341","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a degenerative respiratory condition characterized by significant mortality rates and a scarcity of available treatment alternatives. Cuproptosis, a novel form of copper-induced cell death, has garnered attention for its potential implications. The study aimed to explore the diagnostic value of cuproptosis-related hub genes in patients with IPF. Additionally, multiple bioinformatics analyses were employed to identify immune-related biomarkers associated with the diagnosis of IPF, offering valuable insights for future treatment strategies.</p><p><strong>Methods: </strong>Four microarray datasets were selected from the Gene Expression Omnibus (GEO) collection for screening. Differentially expressed genes (DEGs) associated with IPF were analyzed. Additionally, weighted gene coexpression network analysis (WGCNA) was employed to identify the DEGs most associated with IPF. Ultimately, we analyzed five cuproptosis-related hub genes and assessed their diagnostic value for IPF in both the training and validation sets. Additionally, four immune-related hub genes were screened using a protein-protein interaction (PPI) network and evaluated through the receiver operating characteristic (ROC) curve. Lastly, single-cell RNA-seq was employed to further investigate differential gene distribution.</p><p><strong>Results: </strong>We identified a total of 92 DEGs. Bioinformatics analysis highlighted five cuproptosis-related genes as candidate biomarkers, including three upregulated genes (<i>CFH</i>, <i>STEAP1</i>, and <i>HDC</i>) and two downregulated genes (<i>NUDT16</i> and <i>FMO5</i>). The diagnostic accuracy of these five genes in the cohort was confirmed to be reliable. Additionally, we identified four immune-related hub genes that demonstrated strong diagnostic performance for IPF, with <i>CXCL12</i> showing an AUROC of 0.90. We also examined the relationship between these four genes and immune cells. <i>CXCL12</i> was significantly negatively associated with neutrophils, while <i>CXCR2</i> was associated exclusively with neutrophils, consistent with our single-cell sequencing results. <i>CTSG</i> showed a primarily positive association with follicular helper T, and <i>SPP1</i> was most strongly associated with macrophages. Finally, our single-cell sequencing data revealed that in patients with IPF, <i>CXCL12</i> was highly expressed in the endothelial cell subset (ECs), while <i>SPP1</i> exhibited high expression in multiple cellular populations. The expression of the <i>CTSG</i> showed statistically significant differences in monocyte macrophages.</p><p><strong>Conclusion: </strong>The research methodically depicted the intricate interplay among five cuproptosis-related genes, four immune-related hub genes, and IPF, offering new ideas for diagnosing and treating patients with IPF.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1458341"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482782","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":"CD109, a master regulator of inflammatory responses.","authors":"Adel Batal, Setareh Garousi, Kenneth W Finnson, Anie Philip","doi":"10.3389/fimmu.2024.1505008","DOIUrl":"10.3389/fimmu.2024.1505008","url":null,"abstract":"<p><p>Inflammation is a complex response to harmful stimuli, crucial for immunity, and linked to chronic diseases and cancer, with TGF-β and NF-κB pathways as key regulators. CD109 is a glycosylphosphatidylinositol (GPI)-anchored protein, that our group has originally identified as a TGF-β co-receptor and inhibitor of TGF-β signaling. CD109 modulates TGF-β and NF-κB pathways, to influence immune responses and inflammation. CD109's multifaceted role in inflammation spans various tissue types, including the skin, lung, bone and bone-related tissues, and various types of cancers. CD109 exerts its effects by modulating processes such as cytokine secretion, immune cell recruitment, macrophage polarization, T helper cell function and cancer cell phenotype and function. Here, we review CD109's regulatory functions in inflammatory responses in these various tissues and cell types. Exploration of CD109's mechanisms of action will enhance our understanding of its contributions to disease pathology and its potential for therapeutic applications.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"15 ","pages":"1505008"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482833","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 DNA in atherosclerosis research progress: a mini review.","authors":"Zheng Liu, Nan Huang, Chan Liu, Can Wu, Ling Zhou, Xiang Liu, Haibo Lei","doi":"10.3389/fimmu.2025.1526390","DOIUrl":"10.3389/fimmu.2025.1526390","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic inflammatory disease that primarily affects large and medium-sized arteries and is one of the leading causes of death worldwide. This article reviews the multifaceted role of mitochondrial DNA (mtDNA) in AS, including its structure, function, release, and relationship with inflammation. Damage and release of mtDNA are considered central drivers in the development of AS, as they participate in the progression of AS by activating inflammatory pathways and affecting lipid metabolism. Therefore, therapeutic strategies targeting mtDNA and its downstream effects may provide new avenues to address this global health challenge.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1526390"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482761","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":"Single-cell RNA sequencing of circulating immune cells supports inhibition of <i>TNFAIP3</i> and <i>NFKBIA</i> translation as psoriatic arthritis biomarkers.","authors":"Ameth N Garrido, Rohan Machhar, Omar F Cruz-Correa, Darshini Ganatra, Sarah Q Crome, Joan Wither, Igor Jurisica, Dafna D Gladman","doi":"10.3389/fimmu.2025.1483393","DOIUrl":"10.3389/fimmu.2025.1483393","url":null,"abstract":"<p><strong>Objective: </strong>To identify biomarkers that distinguish psoriatic arthritis (PsA) from cutaneous psoriasis without arthritis (PsC) and healthy controls (HC) using single cell RNA sequencing (scRNA-seq).</p><p><strong>Method: </strong>Peripheral blood mononuclear cell samples from three patients with PsA fulfilling CASPAR criteria, three patients with PsC and two HC were profiled using scRNA-seq. Differentially expressed genes (DEGs) identified through scRNA-seq were validated on classical monocytes, and CD4⁺ and CD8⁺ T cell subsets derived from an independent cohort of patients using the NanoString nCounter^® platform. Protein expression was measured in CD4⁺ and CD8⁺ T cells by immunoblotting.</p><p><strong>Results: </strong>A total of 18 immune cell population clusters were identified. Across 18 cell clusters, we identified 234 DEGs. <i>NFKBIA</i> and <i>TNFAIP3</i> were overexpressed in PsA vs HC and PsC patients. Immunoblotting of the proteins encoded in these genes (IκBα and A20, respectively) showed higher levels in PsA CD4⁺ T cells compared to HC. Conversely, lower levels were observed in PsA CD8⁺ T cell lysates compared to HC for both proteins.</p><p><strong>Conclusion: </strong>These results suggest that translation of <i>TNFAIP3</i> and <i>NFKBIA</i> may be inhibited in PsA CD8⁺ T cells. This study provides insight into the cellular heterogeneity of PsA, showing that non-cell type specific expression of genes associated with the disease can be dysregulated through different mechanisms in distinct cell types.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1483393"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482851","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":"Corrigendum: The role of dendritic cells in tertiary lymphoid structures: implications in cancer and autoimmune diseases.","authors":"Mariana Reste, Kristi Ajazi, Ayca Sayi-Yazgan, Radmila Jankovic, Biljana Bufan, Sven Brandau, Espen S Bækkevold, Florent Petitprez, Malin Lindstedt, Gosse J Adema, Catarina R Almeida","doi":"10.3389/fimmu.2025.1538818","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1538818","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2024.1439413.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1538818"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482803","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":"Corrigendum: The phytohormone abscisic acid enhances remyelination in mouse models of multiple sclerosis.","authors":"Femke Van Gaever, Fleur Mingneau, Sam Vanherle, Yasmine Driege, Mira Haegman, Elien Van Wonterghem, Junhua Xie, Roosmarijn E Vandenbroucke, Jerome J A Hendriks, Rudi Beyaert, Jens Staal","doi":"10.3389/fimmu.2025.1562292","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1562292","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2024.1500697.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1562292"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482798","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":"Adjuvanted subunit intranasal vaccine reduces SARS-CoV-2 onward transmission in hamsters.","authors":"Yongjun Sui, Swagata Kar, Bhavna Chawla, Tanya Hoang, YuanKai Yu, Shannon M Wallace, Hanne Andersen, Jay A Berzofsky","doi":"10.3389/fimmu.2025.1514845","DOIUrl":"10.3389/fimmu.2025.1514845","url":null,"abstract":"<p><strong>Introduction: </strong>Most COVID-19 vaccine trials have focused on recipient protection, not protection of their contacts, a critical need. As a subunit intranasal COVID-19 vaccine reduced nasopharyngeal virus more than did an intramuscular (IM) vaccine, we hypothesized that this vaccine might reduce onward transmission to others.</p><p><strong>Methods: </strong>We vaccinated hamsters with either the IM-administrated licensed mRNA vaccine twice or one dose of mRNA IM followed by adjuvanted subunit intranasal vaccine. 24 hours after SARS-CoV-2 challenge, these animals were housed with naïve recipients in a contactless chamber that allows airborne transmission.</p><p><strong>Results: </strong>Onward airborne transmission was profoundly blocked: the donor and recipients of the intranasal vaccine-boosted group had lower oral and lung viral loads (VL), which correlated with mucosal ACE2 inhibition activity. Notably, in this head-to-head comparison of COVID-19 booster vaccines on SARS-CoV-2 onward transmission, we found that statistically significant viral reduction in the lung tissues and oral swabs was observed only in the intranasal S1 nanoparticle vaccine-boosted group, but not in the systemic mRNA vaccine-boosted group, suggesting the superior protection of this intranasal vaccine, which could act as an attractive vaccine booster candidate to complement the current licensed systemic vaccines.</p><p><strong>Discussion: </strong>Overall, our study strongly supports the use of the intranasal vaccine as a boost to protect not only the vaccinated person, but also people exposed to the vaccinated person, a key public health goal.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1514845"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467715","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":"Bradykinin B1 receptor signaling triggers complement activation on endothelial cells.","authors":"Ingrid Lopatko Fagerström, Alexandra Gerogianni, Markus Wendler, Ida Arvidsson, Ashmita Tontanahal, Ann-Charlotte Kristoffersson, Fatimunnisa Qadri, Michael Bader, Diana Karpman","doi":"10.3389/fimmu.2025.1527065","DOIUrl":"10.3389/fimmu.2025.1527065","url":null,"abstract":"<p><strong>Introduction: </strong>The complement and kallikrein-kinin systems (KKS) are both activated during vascular inflammation, and there are many known interactions between the two systems. This study investigated if KKS activation induced complement activation on endothelial cells, and if activation was dependent on bradykinin B1 receptor (B1R) signaling.</p><p><strong>Methods: </strong>KKS was activated in normal human serum by kaolin or activated factor XII (FXIIa). ADP-preactivated primary glomerular endothelial cells (PGECs) were incubated with serum, with or without kaolin or FXIIa, and with or without the B1R antagonist (R715) or the inositol triphosphate receptor (IP3R) inhibitor 2-aminoethoxydiphenyl borate (2-APB). Complement factors C3a, factor Ba and C5b-9 were evaluated by ELISA or immunoblotting. B1/B2 receptor double knock-out and wild-type mice were injected with lipopolysaccharide from <i>E. coli</i> B5:O55, to induce KKS activation.</p><p><strong>Results: </strong>Supernatants from PGECs incubated with serum exposed to kaolin or FXIIa exhibited higher levels of Ba and C5b-9, which were significantly reduced in the presence of the B1R antagonist. Complement activation induced by FXIIa was also reduced in the presence of the IP3R inhibitor. Likewise, cell lysates showed higher levels of C3a and C5b-9 in the presence of kaolin and FXIIa, and complement activation was significantly reduced in the presence of the B1R antagonist. B1/B2 receptor double knock-out mice exhibited less C3 and C5b-9 deposition in glomeruli compared to wild-type mice.</p><p><strong>Conclusion: </strong>This study demonstrates that KKS activation contributes to complement activation on the endothelium by B1R signaling. Blocking the B1R may have a role in reducing complement deposition and its effects on the endothelium.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1527065"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482775","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":"Commensal bacteria education history calibrates the naivety and activation threshold of adaptive antiviral immune system.","authors":"Baohua Li, Zhou Sha, Li Mou, Feng Zhang, Lifeng Jia, Yan Zhu, Yan Guo, Guohong Deng, Haibo Wu, Hong Wei, Yuzhang Wu, Lilin Ye, Changjiang Liu, Jian Li, Yanyan Zhang","doi":"10.3389/fimmu.2025.1519023","DOIUrl":"10.3389/fimmu.2025.1519023","url":null,"abstract":"<p><p>Exhaustion of the immune system's ability to adapt to novelty suggests that the changes it undergoes might be a consequence of an evolutionary unpredictable antigenic exposure over a lifetime. Thus, we raise the question of whether a naive immune system can manage new antigens better than an educated immune system. Here, by employing the naive immune system of germ-free (GF) mice without a history of microbial exposure, we compared their adaptive immune responses with those of the conventional (Conv) mice upon new viral infection. Interestingly, the naive GF immune system showed robust T-cell responses, with more potent memory T cells established for long-term protection, even in the condition of primary lower T-cell levels for naive GF mice. Furthermore, we found that the ABX-treated Conv mice showed impaired T-cell responses, compared with the untreated Conv ones. With the microbiota eliminated, the ABX mice still have a history of microbial exposure and education for their immune system. In summary, commensal bacteria education history calibrates the naivety and the activation threshold of the adaptive antiviral immune system.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1519023"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482776","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":"Quantitative N-glycoproteomic analysis reveals glycosylation signatures of plasma immunoglobulin G in systemic sclerosis.","authors":"Lu Cheng, Yanhong Li, Yu Zhou, Yingying Ling, Tong Wu, Zongan Liang, Yinlan Wu, Chunyu Tan, Yi Liu, Yong Zhang","doi":"10.3389/fimmu.2025.1531191","DOIUrl":"10.3389/fimmu.2025.1531191","url":null,"abstract":"<p><p>Systemic sclerosis (SSc) is a perplexing autoimmune disorder, characterized by mysterious causes, high mortality rates, and a lack of effective treatments. The role of abnormal glycosylation in the onset of autoimmune diseases has been recognized for some time. Nonetheless, the intricate details of intact glycopeptides in SSc remain elusive owing to challenges in their detection. In this study, we characterized plasma immunoglobulin G (IgG) intact N-glycopeptides from 30 SSc patients and 30 healthy controls (HCs) via our recently developed intact glycopeptide analysis method GlycoQuant. Through this approach, twelve differentially expressed intact N-glycopeptides were identified. The correlation of specific intact N-glycopeptides with the clinical features of SSc patients was analyzed. The results revealed a notable increase in the levels of 6 intact N-glycopeptides (IgG2-N3H3F1, IgG2-N3H4F1, IgG2-N4H4F1, IgG2-N4H5F1, IgG2-N5H4F1, and IgG2-N5H5F1) and a decrease in the levels of another set of 6 intact N-glycopeptides (IgG1-N4H3F1, IgG2-N3H6F1A1, IgG2-N4H4F1A1, IgG2-N5H3F1, IgG3-N4H3F1, and IgG3-N4H4F1). These changes in the levels of intact N-glycopeptides are associated with various aspects of SSc, including diffuse SSc (dSSc), interstitial lung disease (ILD), disease progression, cardiovascular involvement and C-reactive protein in the peripheral blood. In summary, this study offers a detailed overview of the intact N-glycopeptide profile in the peripheral blood of patients with SSc, providing valuable insights that could propel further research into SSc.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1531191"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482850","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}