Journal of Immunology Research最新文献

{"title":"Exosome-Derived microRNA: Potential Target for Diagnosis and Treatment of Sepsis.","authors":"Yujie Xiao, Yixuan Yuan, Dahai Hu, Hongtao Wang","doi":"10.1155/2024/4481452","DOIUrl":"10.1155/2024/4481452","url":null,"abstract":"<p><p>Exosome-derived microRNAs (miRNAs) are emerging as pivotal players in the pathophysiology of sepsis, representing a new frontier in both the diagnosis and treatment of this complex condition. Sepsis, a severe systemic response to infection, involves intricate immune and nonimmune mechanisms, where exosome-mediated communication can significantly influence disease progression and outcomes. During the progress of sepsis, the miRNA profile of exosomes undergoes notable alterations, is reflecting, and may affect the progression of the disease. This review comprehensively explores the biology of exosome-derived miRNAs, which originate from both immune cells (such as macrophages and dendritic cells) and nonimmune cells (such as endothelial and epithelial cells) and play a dynamic role in modulating pathways that affect the course of sepsis, including those related to inflammation, immune response, cell survival, and apoptosis. Taking into account these dynamic changes, we further discuss the potential of exosome-derived miRNAs as biomarkers for the early detection and prognosis of sepsis and advantages over traditional biomarkers due to their stability and specificity. Furthermore, this review evaluates exosome-based therapeutic miRNA delivery systems in sepsis, which may pave the way for targeted modulation of the septic response and personalized treatment options.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"4481452"},"PeriodicalIF":3.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893600","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}

{"title":"Breastfeeding and Neonatal Age Influence Neutrophil-Driven Ontogeny of Blood Cell Populations in the First Week of Human Life.","authors":"Sebastiano Montante, Rym Ben-Othman, Nelly Amenyogbe, Asimenia Angelidou, Anita van den Biggelaar, Bing Cai, Yixuan Chen, Alansana Darboe, Joann Diray-Arce, Rebecca Ford, Olubukola Idoko, Amy Lee, Mandy Lo, Kerry McEnaney, Mehrnoush Malek, David Martino, Geraldine Masiria, Oludare A Odumade, William Pomat, Casey Shannon, Kinga Smolen, The Epic Consortium, Al Ozonoff, Peter Richmond, Scott Tebbutt, Ofer Levy, Beate Kampmann, Ryan Brinkman, Tobias Kollmann","doi":"10.1155/2024/1117796","DOIUrl":"10.1155/2024/1117796","url":null,"abstract":"<p><p>The first few days of life are characterized by rapid external and internal changes that require substantial immune system adaptations. Despite growing evidence of the impact of this period on lifelong immune health, this period remains largely uncharted. To identify factors that may impact the trajectory of immune development, we conducted stringently standardized, high-throughput phenotyping of peripheral white blood cell (WBC) populations from 796 newborns across two distinct cohorts (The Gambia, West Africa; Papua New Guinea, Melanesia) in the framework of a Human Immunology Project Consortium (HIPC) study. Samples were collected twice from each newborn during the first week of life, first at Day of Life 0 (at birth) and then subsequently at Day of Life 1, 3, or 7 depending on the randomization group the newborn belongs to. The subsequent analysis was conducted at an unprecedented level of detail using flow cytometry and an unbiased automated gating algorithm. The results showed that WBC composition in peripheral blood changes along patterns highly conserved across populations and environments. Changes across days of life were most pronounced in the innate myeloid compartment. Breastfeeding, and at a smaller scale neonatal vaccination, were associated with changes in peripheral blood neutrophil and monocyte cell counts. Our results suggest a common trajectory of immune development in newborns and possible association with timing of breastfeeding initiation, which may contribute to immune-mediated protection from infection in early life. These data begin to outline a specific window of opportunity for interventions that could deliberately direct WBC composition, and with that, immune trajectory and thus ontogeny in early life. This trial is registered with NCT03246230.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"1117796"},"PeriodicalIF":3.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855674","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}

{"title":"Methazolamide Can Treat Atherosclerosis by Increasing Immunosuppressive Cells and Decreasing Expressions of Genes Related to Proinflammation, Calcification, and Tissue Remodeling.","authors":"Hongji Zhou, Rui Zhang, Min Li, Fuyan Wang, Yuxia Gao, Kehua Fang, Jinbao Zong, Xiaotian Chang","doi":"10.1155/2024/5009637","DOIUrl":"10.1155/2024/5009637","url":null,"abstract":"<p><p>It has been reported that carbonic anhydrase I (CA1) is a target for the diagnosis and therapy of atherosclerosis (AS) since CA1 can promote AS aortic calcification. We also found that methazolamide (MTZ), a drug for glaucoma treatment and an inhibitor of carbonic anhydrases, can treat AS by inhibiting calcification in aortic tissues. This study focused on the therapeutic mechanism of MTZ and the pathogenic mechanism of AS. In this study, a routine AS animal model was established in ApoE-/- mice, which were treated with MTZ. The aortic tissues were analyzed using single-cell sequencing. MTZ significantly increased the proportions of B-1/MZB B cells with high expressions of Nr4A1 and Ccr7, CD8+CD122+ Treg-like cells with high Nr4A1 expression, and smooth muscle cells with high Tpm2 expression. These cells or their marker genes were reported to exert immunosuppressive, anti-proinflammatory, and atheroprotective effects. MTZ also decreased the proportions of endothelial cells with high expressions of Retn, Apoc1, Lcn2, Mt1, Serpina3, Lpl, and Lgals3; nonclassical CD14+CD16++ monocytes with high expressions of Mt1, Tyrobp, Lgals3, and Cxcl2; and Spp1+ macrophages with high expressions of Mmp-12, Trem2, Mt1, Lgals3, Cxcl2, and Lpl. These cells or their marker genes have been reported to promote inflammation, calcification, tissue remodeling, and atherogenesis. A significant decrease in the proportion of CD8+CD183 (CXCR3)+ T cells, the counterpart of murine CD8+CD122+ T cells, was detected in the peripheral blood of newly diagnosed AS patients rather than in that of patients receiving anti-AS treatments. These results suggest that MTZ can treat AS by increasing immunosuppressive cells and decreasing expressions of genes related to inflammation, calcification, and tissue remodeling.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"5009637"},"PeriodicalIF":3.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855675","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}

{"title":"Impaired Proliferation of CD8⁺ T Cells Stimulated with Monocyte-Derived Dendritic Cells Previously Matured with Thapsigargin-Stimulated LAD2 Human Mast Cells.","authors":"Katerina Kalkusova, Pavla Taborska, Dmitry Stakheev, Michal Rataj, Sindija Smite, Elea Darras, Julia Albo, Jirina Bartunkova, Luca Vannucci, Daniel Smrz","doi":"10.1155/2024/5537948","DOIUrl":"10.1155/2024/5537948","url":null,"abstract":"<p><p>CD8⁺ T cells are essential for adaptive immunity against infection and tumors. Their ability to proliferate after stimulation is crucial to their functionality. Dendritic cells (DCs) are professional antigen-presenting cells that induce their proliferation. Here, we show that thapsigargin-induced LAD2 mast cell (MC) line-released products can impair the ability of monocyte-derived DCs to induce CD8⁺ T-cell proliferation and the generation of Th1 cytokine-producing T cells. We found that culture medium conditioned with LAD2 MCs previously stimulated with thapsigargin (thapsLAD2) induces maturation of DCs as determined by the maturation markers CD80, CD83, CD86, and HLA-DR. However, thapsLAD2-matured DCs produced no detectable TNF<i>α</i> or IL-12 during the maturation. In addition, although their surface expression of PD-L1 was comparable with the immature or TLR7/8-agonist (R848)-matured DCs, their TIM-3 expression was significantly higher than in immature DCs and even much higher than in R848-matured DCs. In addition, contrary to R848-matured DCs, the thapsLAD2-matured DCs only tended to induce enhanced proliferation of CD4⁺ T cells than immature DCs. For CD8⁺ T cells, this tendency was not even detected because thapsLAD2-matured and immature DCs comparably induced their proliferation, which contrasted with the significantly enhanced proliferation induced by R848-matured DCs. Furthermore, these differences were comparably recapitulated in the ability of the tested DCs to induce IFN<i>γ</i>- and IFN<i>γ</i>/TNF<i>α</i>-producing T cells. These findings show a novel mechanism of MC-mediated regulation of adaptive immune responses.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"5537948"},"PeriodicalIF":3.5,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759172","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}

{"title":"C5aR2 Deficiency Lessens C5aR1 Distribution and Expression in Neutrophils and Macrophages.","authors":"Ting Zhang, Ning Ma, Jiaxing Wang, Xiaoyun Min, Linlin Wei, Ke Li","doi":"10.1155/2024/2899154","DOIUrl":"10.1155/2024/2899154","url":null,"abstract":"<p><p>As another receptor for complement activation product C5a, C5aR2 has been paid much attention these years. Although controversial and complex, its specific signals or roles in modulating the classic receptor C5aR1 have been investigated and gradually revealed. The hypothesis of the heterodimer of C5aR1 and C5aR2 has also been suggested and observed under extremely high C5a concentrations. In this article, we tried to investigate whether C5aR2 would affect C5aR1 expression under normal or inflammatory conditions in WT and <i>C5ar2</i> ^<i>-/</i>- mice of C57BL/6 background. We focused on the innate immune cells-neutrophils and macrophages. The mRNA levels of <i>C5ar1</i> in normal kidney, liver, and the mRNA or protein levels of naïve-bone marrow and peripheral blood leukocytes and peritoneal M<i>φ</i>s were comparable between WT and <i>C5ar2</i> ^<i>-/</i>- mice, indicating the technique of C5aR2 knockout did not affect the transcription of its neighboring gene C5aR1. However, the mean fluorescence intensity of surface C5aR1 on naïve circulating <i>C5ar2</i> ^<i>-/</i>- neutrophils detected by FACS was reduced, which might be due to the reduced internalization of C5aR1 on <i>C5ar2</i> ^<i>-/</i>- neutrophils. In the peritonitis model induced by <i>i.p</i>. injection of thioglycollate, more neutrophils were raised after 10 hr in <i>C5ar2</i> ^<i>-/</i>- peritoneal cavity, indicating the antagonism of C5aR2 on C5aR1 signal in neutrophil chemotaxis. After 3 days of thioglycollate injection, the mainly infiltrating macrophages were comparable between WT and <i>C5ar2</i> ^<i>-/</i>- mice, but the <i>C5ar1</i> mRNA and surface or total C5aR1 protein expression were both reduced in <i>C5ar2</i> ^<i>-/</i>- macrophages, combined with our previous study of reduced chemokines and cytokines expression in <i>C5ar2</i> ^<i>-/</i>- peritoneal macrophages, indicating that C5aR2 in macrophages may cooperate with C5aR1 inflammatory signals. Our article found C5aR2 deficiency lessened C5aR1 distribution and expression in neutrophils and macrophages with different functions, indicating C5aR2 might function differently in different cells.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"2899154"},"PeriodicalIF":3.5,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633741","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}

{"title":"Characterizing the Tumor Microenvironment and Its Correlation with cDC1-Related Gene Expression in Gastric Cancer.","authors":"Song-Hee Han, Mi Ha Ju","doi":"10.1155/2024/4468145","DOIUrl":"10.1155/2024/4468145","url":null,"abstract":"<p><strong>Materials and methods: </strong>We analyzed RNA-seq data from the Cancer Genome Atlas (TCGA-STAD) and Gene Expression Omnibus (GEO) datasets, focusing on five cDC1-related genes. The cDC1-related signature was defined and divided into high and low expression groups. We employed gene set variation analysis (GSVA) for oncogenic signaling pathways and conducted comprehensive statistical analyses, including Kaplan-Meier and Cox proportional hazards models.</p><p><strong>Results: </strong>The high cDC1-related gene signature group was associated with poorer overall and disease-free survival in the TCGA-STAD cohort. Significant differences in CD8+ T cell infiltration and cytotoxic capabilities were observed between high and low CDC1-related signature groups. The study also revealed a strong correlation between CDC1-related signature and increased expression of immune checkpoint proteins and oncogenic pathways, suggesting a complex immunosuppressive tumor microenvironment.</p><p><strong>Conclusions: </strong>Our findings indicate the potential of the cDC1-related signature as a prognostic marker in GC, offering insights into the tumor-immune interplay. The study underscores the importance of cDC1s in shaping the tumor microenvironment and their influence on patient prognosis in GC. These results may contribute to the development of novel therapeutic strategies targeting the immune microenvironment in GC.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"4468145"},"PeriodicalIF":3.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626913","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}

{"title":"PD-L2 Expression in Breast Cancer Promotes Tumor Development and Progression.","authors":"Yuling Sun, Jie Yang, Yachun Chen, Yundi Guo, Jian Xiong, Xuqin Guo, Yawen Zhang, Li Gu, Min Tong, Weipeng Wang, Jing Sun","doi":"10.1155/2024/3145695","DOIUrl":"10.1155/2024/3145695","url":null,"abstract":"<p><strong>Background: </strong>This work focused on investigating the role of programmed death ligand 2 (PD-L2) in the progression of breast cancer by utilizing breast cancer specimens and cells.</p><p><strong>Materials and methods: </strong>The serum levels of soluble PD-L2 (sPD-L2) in breast cancer patients and healthy individuals were analyzed by means of the enzyme-linked immunosorbent assay, and the PD-L2 levels within 416 resected breast cancer specimens were assessed through immunohistochemistry. Concurrently, in vitro cell experiments and in vivo animal experiments were carried out to analyze the relationship between PD-L2 and the invasion and migration of breast cancer.</p><p><strong>Results: </strong>The concentration of sPD-L2 in breast cancer patients significantly increased compared to that in the control groups. Additionally, breast cancer patients with high concentrations of sPD-L2 had higher Ki67 values (≥30%) and tumor grades. PD-L2 was expressed in 79.09% of the cancer samples, which exhibited a positive correlation with the progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2). Furthermore, we discovered that knockdown of PD-L2 inhibited the migratory and invasive abilities of both MCF-7 and MDA-MB231 cells.</p><p><strong>Conclusion: </strong>Our findings demonstrated that knockdown of PD-L2 suppressed tumor growth, providing novel insights into important biological functions.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"3145695"},"PeriodicalIF":3.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563506","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}

{"title":"12,13-diHOME Promotes Inflammatory Macrophages and Epigenetically Modifies Their Capacity to Respond to Microbes and Allergens.","authors":"Din L Lin, Kevin M Magnaye, Cara E Porsche, Sophia R Levan, Elze Rackaityte, Mustafa Özçam, Susan V Lynch","doi":"10.1155/2024/2506586","DOIUrl":"10.1155/2024/2506586","url":null,"abstract":"<p><p>Elevated infant fecal concentrations of the bacterial-derived lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) increase the risk for childhood atopy and asthma. However, the mechanisms by which this lipid contributes to disease development are largely unknown. We hypothesized that macrophages, which are key to both antimicrobial and antigen responses, are functionally and epigenetically modified by 12,13-diHOME leading to short- and long-term dysfunction with consequences for both antimicrobial and antigenic responses. Macrophages exposed to 12,13-diHOME are skewed toward inflammatory IL-1<i>β</i> ^highCD206^low cells, a phenomenon that is further amplified in the presence of common microbial-, aero-, and food-allergens. These IL-1<i>β</i> ^highCD206^low macrophages also exhibit reduced bacterial phagocytic capacity. In primary immune cell coculture assays involving peanut allergen stimulation, 12,13-diHOME promotes both IL-1<i>β</i> and IL-6 production, memory B cell expansion, and increased IgE production. Exposure to 12,13-diHOME also induces macrophage chromatin remodeling, specifically diminishing access to interferon-stimulated response elements resulting in reduced interferon-regulated gene expression upon bacterial lipopolysaccharide stimulation. Thus 12,13-diHOME reprograms macrophage effector function, B-cell interactions and promotes epigenetic modifications that exacerbate inflammatory response to allergens and mutes antimicrobial response along the interferon axis. These observations offer plausible mechanisms by which this lipid promotes early-life pathogenic microbiome development and innate immune dysfunction associated with childhood allergic sensitization.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"2506586"},"PeriodicalIF":3.5,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554988","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}

{"title":"Circular RNA CircZNF644 Facilitates Circulating Follicular Helper T Cells Response in Patients with Graves' Disease.","authors":"Yingzhao Liu, Xuehua Wang, Juan Xu, Qian Xu, Jie Xing, Junli Zou, Shengjun Wang, Huiyong Peng","doi":"10.1155/2024/9527268","DOIUrl":"10.1155/2024/9527268","url":null,"abstract":"<p><p>Aberrant accumulation of circulating follicular helper T cells (cTfh) has been found in the peripheral blood mononuclear cells (PBMCs) of Graves' disease (GD) patients. However, the underlying mechanism that contributes to the imbalance of cTfh cells remains unknown. Previously, studies described a GD-related circular RNAs (circRNAs)-circZNF644 that might be associated with cTfh cells. This study aimed to investigate the role of circZNF644 on cTfh cells in GD patients. Here, we found that circZNF644 was highly stable expression in the PBMCs of GD patients, which was positively correlated with the serum levels of TSH receptor autoantibodies (TRAb). Knockdown of circZNF644 caused a reduction of the proportion of cTfh cells in vitro. Mechanistically, circZNF644 served as a ceRNA for miR-29a-3p to promote ICOS expression, resulting in increased cTfh cells. In the PBMCs of GD patients, circZNF644 expression was positively correlated with ICOS expression and the percentage of cTfh cells, but negatively related to miR-29a-3p expression. Additionally, a strong relationship between circZNF644 and IL-21 was revealed in GD patients, and silencing of circZNF644 inhibited IL-21 expression. Our study elucidated that elevated expression of circZNF644 is a key feature in the development of GD and may contribute to the pathogenic role of cTfh cells in GD.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"9527268"},"PeriodicalIF":3.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534507","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}

{"title":"CCR7 and CD48 as Predicted Targets in Acute Rejection Related to M1 Macrophage after Pediatric Kidney Transplantation.","authors":"Jie Zhang, Jun Pei, Chengjun Yu, Jin Luo, Yifan Hong, Yi Hua, Guanghui Wei","doi":"10.1155/2024/6908968","DOIUrl":"10.1155/2024/6908968","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplantation (KT) is the best treatment for end-stage renal disease. Although long and short-term survival rates for the graft have improved significantly with the development of immunosuppressants, acute rejection (AR) remains a major risk factor attacking the graft and patients. The innate immune response plays an important role in rejection. Therefore, our objective is to determine the biomarkers of congenital immunity associated with AR after KT and provide support for future research.</p><p><strong>Materials and methods: </strong>A differential expression genes (DEGs) analysis was performed based on the dataset GSE174020 from the NCBI gene Expression Synthesis Database (GEO) and then combined with the GSE5099 M1 macrophage-related gene identified in the Molecular Signatures Database. We then identified genes in DEGs associated with M1 macrophages defined as DEM1Gs and performed gene ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Cibersort was used to analyze the immune cell infiltration during AR. At the same time, we used the protein-protein interaction (PPI) network and Cytoscape software to determine the key genes. Dataset, GSE14328 derived from pediatric patients, GSE138043 and GSE9493 derived from adult patients, were used to verify Hub genes. Additional verification was the rat KT model, which was used to perform HE staining, immunohistochemical staining, and Western Blot. Hub genes were searched in the HPA database to confirm their expression. Finally, we construct the interaction network of transcription factor (TF)-Hub genes and miRNA-Hub genes.</p><p><strong>Results: </strong>Compared to the normal group, 366 genes were upregulated, and 423 genes were downregulated in the AR group. Then, 106 genes related to M1 macrophages were found among these genes. GO and KEGG enrichment analysis showed that these genes are mainly involved in cytokine binding, antigen binding, NK cell-mediated cytotoxicity, activation of immune receptors and immune response, and activation of the inflammatory NF-<i>κ</i>B signaling pathway. Two Hub genes, namely CCR7 and CD48, were identified by PPI and Cytoscape analysis. They have been verified in external validation sets, originated from both pediatric patients and adult patients, and animal experiments. In the HPA database, CCR7 and CD48 are mainly expressed in T cells, B cells, macrophages, and tissues where these immune cells are distributed. In addition to immunoinfiltration, CD4+T, CD8+T, NK cells, NKT cells, and monocytes increased significantly in the AR group, which was highly consistent with the results of Hub gene screening. Finally, we predicted that 19 TFs and 32 miRNAs might interact with the Hub gene.</p><p><strong>Conclusions: </strong>Through a comprehensive bioinformatic analysis, our findings may provide predictive and therapeutic targets for AR after KT.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"6908968"},"PeriodicalIF":3.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492245","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}