Immunobiology最新文献

{"title":"B lymphocytes impair osteogenesis by inhibiting BMSC differentiation in osteoporosis","authors":"Cong Peng ,&nbsp;Qiao Yang ,&nbsp;Linyu Li ,&nbsp;Yufeng Li ,&nbsp;Zhaoyang Ye ,&nbsp;Kun Zhao ,&nbsp;Yi Yi ,&nbsp;Liang Wang","doi":"10.1016/j.imbio.2025.153094","DOIUrl":"10.1016/j.imbio.2025.153094","url":null,"abstract":"<div><div><strong>Background:</strong> B lymphocytes have been implicated in the inhibition of osteogenesis, but their role in osteoporosis (OP) remains unclear. This study investigates the association between B lymphocytes and impaired osteogenesis in OP patients and explores the underlying mechanisms. <strong>Methods and materials:</strong> A retrospective analysis of 93 patients with OP assessed the relationship between B lymphocyte counts, bone formation marker Procollagen type I N-terminal propeptide (P1NP), and bone mineral density (BMD). An ovariectomy-induced OP mouse model was established. B lymphocytes and bone marrow mesenchymal stem cells (BMSCs) were isolated and co-cultured to evaluate the impact of B lymphocytes on osteogenic differentiation. Transcriptomic profiling and qPCR were performed to identify key regulatory genes. <strong>Results:</strong> Clinically, B lymphocyte counts were significantly elevated in OP patients with impaired osteogenesis (<em>P</em> &lt; 0.05). Receiver operating characteristic (ROC) analysis indicated diagnostic potential (AUC = 0.638, <em>P</em> &lt; 0.05). In vitro, B lymphocytes reduced Alkaline phosphatase (ALP) activity, calcium deposition, and the expression of osteogenic markers (<em>Osterix, Cbfa1</em>) in BMSCs. Transcriptomic analysis identified 210 differentially expressed genes, among which four (<em>Ccdc170, Extl1, Smpd3, and Thsd4</em>) were validated as potential mediators of B cell-induced osteogenesis inhibition. <strong>Conclusion:</strong> B lymphocytes may impair osteogenesis in OP by suppressing BMSC differentiation. These findings highlight B lymphocytes as potential diagnostic markers and therapeutic targets in osteoporosis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153094"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liyan Kaiyin Formula relieves reflux pharyngitis by regulating M1 macrophage polarization via the NF-κB/NLRP3 pathway","authors":"Lirong Wang ,&nbsp;Xuqing Chen ,&nbsp;Tianyu Xu ,&nbsp;Youpeng Fei ,&nbsp;Qi Yang ,&nbsp;Jingjuan An ,&nbsp;Zeqing Li ,&nbsp;Kunmin Wu","doi":"10.1016/j.imbio.2025.153095","DOIUrl":"10.1016/j.imbio.2025.153095","url":null,"abstract":"<div><div><em>Background:</em> We aimed to investigate whether Liyan Kaiyin Formula (LYKYF) can relieve reflux pharyngitis in rats by regulating M1 macrophage polarization <em>via</em> the nuclear factor-κB (NF-κB)/Nod-like receptor protein 3 (NLRP3) pathway.</div><div><em>Methods:</em> Forty rats were randomized into a sham group, a laryngopharyngeal reflux disease (LPRD) group, a LYKYF group and a LYKYF+CHPG group (<em>n</em> = 10). Enzyme-linked immunosorbent assay was conducted to measure the serum levels of inflammatory factors interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α). Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) were performed to measure the expressions of proteins implicated in NF-κB/NLRP3 pathway. Western blotting was also used for the detection of M1 macrophage markers (CD86 and iNOS).</div><div><em>Results:</em> Compared to the sham group, TNF-α, IL-6 and IL-1β levels in the serum, proportion of M1 macrophages in pharyngeal tissues, p-NF-κB p65/p65 ratio, protein expressions of NLRP3, Caspase-1, Apoptosis-associated speck-like protein (ASC), cluster of differentiation 86 (CD86) and inducible nitric oxide synthase, and mRNA expressions of NF-κB p65, NLRP3, Caspase-1 and ASC in the LPRD group exhibited significant elevations (<em>P</em> &lt; 0.05). Compared with the LYKYF group, the LYKYF+CHPG group had significant elevations in serum TNF-α, IL-6 and IL-1β levels, proportion of M1 macrophages in pharyngeal tissues, p-NF-κB p65/p65 ratio, protein expressions of NLRP3, Caspase-1, ASC, CD86 and iNOS, as well as NF-κB p65, NLRP3, Caspase-1 and ASC mRNA expressions (<em>P</em> &lt; 0.05). The identified key target genes were significantly enriched in GO terms associated with signal transduction, protein phosphorylation regulation, and adaptive responses to external stimuli.</div><div><em>Conclusion:</em> LYKYF may suppress M1 macrophage polarization through suppressing the NF-κB/NLRP3 pathway activation, thereby alleviating reflux pharyngitis in rats.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153095"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diversity and hallmarks of metabolites surveyed by MR1","authors":"Emi Ito ,&nbsp;Sho Yamasaki","doi":"10.1016/j.imbio.2025.153091","DOIUrl":"10.1016/j.imbio.2025.153091","url":null,"abstract":"<div><div>Mucosal-associated invariant T (MAIT) cells are one of the innate T cell subset. They are known to contribute to anti-bacterial response by recognizing bacterial components with invariant TCRs which are presented on a monomorphic antigen presenting molecule, MHC related protein 1(MR1). After years of uncertainty about the molecular entity of this bacterial antigen, they were recognized as vitamin B metabolites in 2012, and identified as 5-OP-RU in 2014. Recently, MR1 was found to contain a broad ligand-binding pocket, allowing recognition of compounds with various structures. In this review article, we will summarize the history of MR1 ligand discovery and discuss the potential new ligand structures that may uncover previously-unappreciated MAIT cell functions.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153091"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low peripheral blood B lymphocyte count predicts poor outcome in patients with multiple myeloma","authors":"Yuqi Wang ,&nbsp;Zhongxin Zheng ,&nbsp;Qiaoxi Kang ,&nbsp;Linjing Cai ,&nbsp;Shanshan Zhang ,&nbsp;Huan Chen ,&nbsp;Youhai Yuan ,&nbsp;Hanzhen Zhang ,&nbsp;Xiaolei Wei ,&nbsp;Ru Feng ,&nbsp;Yongqiang Wei","doi":"10.1016/j.imbio.2025.153096","DOIUrl":"10.1016/j.imbio.2025.153096","url":null,"abstract":"<div><div>Previous evidence suggested that B lymphocytes may be involved in the progression and prognosis of multiple myeloma (MM). However, the prognostic value of peripheral B lymphocyte counts on MM before and after treatment in the novel agent era was rarely reported. Herein, we conducted a retrospective study in our center to detect peripheral B lymphocyte counts by flow cytometry in 110 patients with MM and explore the relation with survival. The B lymphocyte count was significantly lower in MM patients than healthy controls (<em>p</em> &lt; 0.005). The cutoff value of B lymphocyte count at diagnosis was 49/μl in MM and 94 patients were divided into in high B lymphocyte group. Patients with low B lymphocyte count had a significant shorter progression-free survival (PFS) (<em>p</em> = 0.025) and a trend of unfavorable overall survival (OS) (<em>p</em> = 0.053) at diagnosis and after 4 cycles' induction treatments. Furthermore, Multivariate analysis showed that low B lymphocyte count at diagnosis independent of ISS stage was a significantly inferior marker for predicting PFS (<em>p</em> = 0.027, hazard ratio(HR) 2.281, 95 % confidence interval (CI) 1.098–4.741) and a trend for OS (<em>p</em> = 0.083, HR 2.394, 95 % CI 0.896–6.160). In summary, these results suggested the low B lymphocyte count was associated with poor outcome in MM patients at diagnosis and after treatment in the novel agent era.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153096"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantification and clustering of immune states in hepatitis B Cirrhosis","authors":"Wei Hou ,&nbsp;Tengxiao Liang ,&nbsp;Fangliang Xing ,&nbsp;Zhongjie Hu","doi":"10.1016/j.imbio.2025.153093","DOIUrl":"10.1016/j.imbio.2025.153093","url":null,"abstract":"<div><h3>Background</h3><div>Hepatitis B Cirrhosis, a severe progression of chronic Hepatitis B infection, requires a comprehensive understanding of the interplay among lymphocyte populations. This study aims to quantify and visualize the relationships among T cells, NK cells, and B cells to aid in assessing immune status, diagnosing the condition, and optimizing treatment strategies.</div></div><div><h3>Methods</h3><div>Peripheral blood samples were collected from 500 patients diagnosed with Hepatitis B Cirrhosis and 500 healthy controls. Sort visualization analysis and three-dimensional numerical fitting were performed to establish a mathematical model describing the relationships among lymphocyte subsets. Self-Organizing Feature Maps (SOFM) were employed for unsupervised clustering to identify distinct immune states.</div></div><div><h3>Results</h3><div>Sort visualization analysis revealed a gradual decrease in T + NK cell levels as B cell levels increased, demonstrating a clear inverse relationship. SOFM clustering identified three distinct clusters with well-defined boundaries. In the 3D lymphocyte plane described by the eq. T percentage =  ‐−0.9879 × B percentage - 1.041 × NK percentage + 97.66, a significant contrast was observed between Hepatitis B Cirrhosis samples and the healthy sample baseline. Analysis across Child-Pugh grades uncovered a cyclical pattern in immune states, reflecting the various stages of the viral infection process.</div></div><div><h3>Conclusions</h3><div>This study provides a quantitative mathematical model and visual representation of lymphocyte population dynamics in Hepatitis B Cirrhosis. The identification of distinct immune states associated with disease progression facilitates the assessment of immunological condition and the optimization of treatment strategies. The integration of immunological and clinical data opens new possibilities for more precise disease staging and personalized.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153093"},"PeriodicalIF":2.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of cytokine expression by E. coli Nissle 1917 and its OMV in intestinal epithelial cell line HT-29","authors":"Seyed Amir Hossein Hamidzadeh ,&nbsp;Asal Katebi ,&nbsp;Leila Hatami-Giklou Jajan ,&nbsp;Farhad Riazi-Rad ,&nbsp;Zahra Tavassol ,&nbsp;Ava Behrouzi","doi":"10.1016/j.imbio.2025.153092","DOIUrl":"10.1016/j.imbio.2025.153092","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is a chronic disease recognized as an autoimmune disorder. The purpose of this is to determine the impact of the <em>E. coli</em> strain <em>Nissle 1917</em> (EcN) and its outer membrane vesicles (OMVs) on cytokine gene expression in an IBD cell line model (HT29) in the hope that these effects will guide the development of interventional therapeutic strategies for IBD. First, the cell viability of HT-29 cells treated with EcN and OMVs was evaluated using the MTT assay. Then, inflamed HT29 cells were inoculated with EcN bacteria (multiplicity of infection (MOI) 10, 100), and extracted OMVs (10, 50 μg/ml). Subsequently, cells were harvested for RNA extraction; followed by expression analysis using real-time PCR and also the evaluation of cytokines by ELISA assay. TNF-α, IL-12, and IL-1β mRNA expression was decreased in EcN bacteria (MOI 10 and 100) and OMV 10 μg/ml group. IL-6 mRNA increased in the MOI 100 of ECN group but decreased in OMV μg/ml, despite elevated IL-6 protein levels in the OMV 50 μg/ml. Notably, no detectable secretion of IL-12, TNF-α, or IL-1β was observed in ELISA assays, suggesting post-transcriptional regulation or low sensitivity. The findings revealed that EcN (MOI 10 and 100) enhanced anti-inflammatory IL-10 production, whereas OMV 10 μg/ml showed superior suppression on mRNA level compared to OMV 50 μg/ml.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153092"},"PeriodicalIF":2.5,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring GIPC2 as a key prognostic marker in colorectal cancer linked to enhanced immune response","authors":"Jiaoyang Gu ,&nbsp;Xing Qi ,&nbsp;Bin Yu ,&nbsp;Yanan Wang ,&nbsp;Liting Zhang ,&nbsp;Shuai Li ,&nbsp;Yu Xin","doi":"10.1016/j.imbio.2025.153090","DOIUrl":"10.1016/j.imbio.2025.153090","url":null,"abstract":"<div><h3>Background</h3><div>Emerging evidence indicates a potential association between aberrant expression of GIPC PDZ Domain Containing Family member 2 (GIPC2) and the progression of colorectal cancer (CRC). However, the detailed characteristics of GIPC2 expression and its prognostic implications in CRC remain to be thoroughly elucidated.</div></div><div><h3>Methods</h3><div>This study retrospectively analyzed the transcriptome profiles and clinical parameters of CRC patients using five publicly available datasets. We used the online database to analyze the prognostic value and subcellular localization of GIPC2 in CRC. Furthermore, comparisons were made between the GIPC2-high and GIPC2-low groups regarding survival prognosis, enriched pathways, genomic mutation status, immune cell infiltration, and TIDE scores using a comprehensive suite of bioinformatics tools. In vitro experiments validated the biological functions of GIPC2 in CRC.</div></div><div><h3>Results</h3><div>The mRNA expression of GIPC2 was significantly lower in CRC samples than in the adjacent mucosa tissues. A negative correlation was observed between GIPC2 expression and tumor mutation burden, microsatellite instability, as well as tumor immune escape. Notably, higher levels of GIPC2 expression were associated with improved survival outcomes in CRC patients. Furthermore, GIPC2 expression was predominantly detected in non-malignant epithelial cells and was closely linked to an enhanced immune response, potentially through the inhibition of extracellular matrix remolding in CRC. Additionally, GIPC2 downregulation could enhance the proliferation, migration, and invasion capabilities of CRC cells in vitro.</div></div><div><h3>Conclusions</h3><div>GIPC2 may serve as a potential prognostic marker for CRC patients. Its expression is significantly correlated with the immune response in CRC.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153090"},"PeriodicalIF":2.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement therapeutics in neurodegenerative diseases","authors":"Wioleta M. Zelek ,&nbsp;Andrea J. Tenner","doi":"10.1016/j.imbio.2025.153089","DOIUrl":"10.1016/j.imbio.2025.153089","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDDs) such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis pose considerable therapeutic challenges, not only due to their complex pathophysiology, but also because any effective drug must be capable of penetrating the brain. Inflammation is a key feature of NDDs. Increasingly, the complement system, long studied in the context of host defence, has emerged as a central player in the brain, with roles extending far beyond its classical immune functions. Complement contributes to synaptic pruning and immune surveillance, but when dysregulated, it can drive chronic inflammation, synapse loss, and neurodegeneration. Complement is also implicated in neurodevelopmental and neuropsychiatric diseases, including schizophrenia and mood disorders, where overactivation of the cascade impacts brain maturation and circuit stability. In this review, we take a broad view of roles of the complement system in both health and disease in the central nervous system (CNS). We summarise key mechanisms through which complement contributes to pathology, discuss emerging therapeutic strategies, and consider major hurdles in CNS drug development, including brain delivery and the need for patient stratification. As our understanding of the pathological roles of the complement system in the brain advances, it is becoming clear that complement therapeutics may offer a novel approach in slowing neurodegeneration, and in addressing a broader spectrum of disorders affecting the brain.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153089"},"PeriodicalIF":2.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced glycation end products induce autophagy in endothelial cells through oxidative stress and regulation of the RhoA-mTOR signaling pathway","authors":"Yan-zhen Li ,&nbsp;Fu-qiu Liang ,&nbsp;Shi-zhu Lin ,&nbsp;Kai Zeng ,&nbsp;Hong-da Cai ,&nbsp;Min Liang","doi":"10.1016/j.imbio.2025.153088","DOIUrl":"10.1016/j.imbio.2025.153088","url":null,"abstract":"<div><h3>Background</h3><div>Advanced glycation end product (AGE)-induced oxidative stress in human umbilical vein endothelial cells (HUVECs) is closely associated with the miR-200b-RhoA signaling axis. Rho-associated protein kinase (RhoA) can crosstalk with the mammalian target of rapamycin (mTOR) complex 1. This study investigated the role of the RhoA-mTOR signaling pathway in autophagy induced in HUVECs by AGEs. In the present study, more severe oxidative damage was found in the HUVECs with AGE-induced autophagy.</div></div><div><h3>Methods</h3><div>We set 5 different concentrations and times respectively, by comparing the cell proliferation changes at different intervention concentrations at each intervention time point and calculating the oxidative stress indicators at four time points, we found that 200 μg/L AGEs intervention for 6 h is the best concentration and time. The expression of RhoA, ROCK, and mTOR was decreased after AGE stimulation, and increased after inhibition of RhoA. Further, we constructed two retroviral plasmids to express constitutively active (Q63LRhoA) or loss-of-function (T19NRhoA) RhoA, and obtained stably transfected HUVECs.</div></div><div><h3>Results</h3><div>There was a statistically significant difference in mTOR mRNA expression between Q63LRhoA and T19NRhoA cells. In summary, AGEs induced oxidative damage and autophagy in HUVECs, which may be related to synchronous regulation of the RhoA-mTOR signaling pathway.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153088"},"PeriodicalIF":2.5,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunophenotypic characteristics of Langhans giant cells and the role of CCR7 in their formation","authors":"Yumeng Jiang ,&nbsp;Yanqing Chen ,&nbsp;Gai Ge ,&nbsp;Zhenzhen Wang ,&nbsp;Yidie Zou ,&nbsp;Haiqin Jiang ,&nbsp;Hongsheng Wang","doi":"10.1016/j.imbio.2025.153086","DOIUrl":"10.1016/j.imbio.2025.153086","url":null,"abstract":"<div><div>Langhans giant cells (LGCs) play a crucial role in granulomatous diseases, yet their unique molecular characteristics and formation mechanisms remain unclear. In this study, we aimed to systematically characterize the molecular features of LGCs and reveal the role of CCR7 in their formation. Mouse bone marrow-derived macrophages (BMDMs) were induced and filtrated to obtain purified LGCs in vitro. RNA sequencing and bioinformatics analysis identified over 3000 differentially expressed genes (DEGs) between LGCs and M0 macrophages, with significant enrichment in cytokine-mediated signaling, extracellular matrix, and cytokine receptor activity. Immunophenotypic analysis revealed elevated expression of antigen-presenting molecules (CD80, CD86, CD40) in LGCs, particularly after <em>Mycobacterium marinum</em> infection. Further investigations demonstrated that CCR7 expression, along with its ligand CCL19, was significantly upregulated at both RNA and protein levels in LGCs compared to M0 macrophages. Small interfering RNA (siRNA) targeting CCR7 led to a marked reduction in LGC formation. Immunohistochemistry confirmed elevated CCR7 expression in LGCs from granuloma model mice and patients with mycobacterial infections. In conclusion, LGCs exhibit distinct molecular characteristics compared to M0 macrophages, with elevated antigen-presenting molecule expression and CCR7 involvement. CCR7 plays a crucial role in LGC formation, providing novel insights into granulomatous disease pathogenesis and potential therapeutic targets.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153086"},"PeriodicalIF":2.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}