Immunobiology最新文献

{"title":"Interleukin 27 (IL-27) in gastrointestinal cancers: from dual roles in tumor immunity to immunotherapeutic opportunities","authors":"Sana Esmaeeli","doi":"10.1016/j.imbio.2026.153214","DOIUrl":"10.1016/j.imbio.2026.153214","url":null,"abstract":"<div><div>Gastrointestinal (GI) cancers continue to account for a major global cancer burden, with immune dysregulation recognized as a key determinant of their initiation and progression. Interleukin-27 (IL-27), a heterodimeric cytokine of the IL-12 family, has emerged as a pivotal but paradoxical regulator of tumor immunity in the GI cancers. IL-27 signals through the WSX-1/gp130 receptor complex, activating signal transducer and activator of transcription (STAT1) - and STAT3-dependent transcriptional pathways, yielding opposing outcomes. STAT1-dominant signaling promotes cytotoxic T-cell proliferation, T helper 1 (Th1) polarization, and natural killer (NK) cell cytotoxicity. However, STAT3-mediated responses induce IL-10, enhances regulatory T (T_reg) cells suppression, stimulates myeloid-derived suppressor cells (MDSCs) activity, and upregulates programmed death ligand 1 (PD-L1), thereby facilitating immune evasion. These contrasting effects manifest in tumor-specific patterns: IL-27 demonstrates potent anti-tumor activity in experimental colorectal (CRC) and pancreatic cancer models, while elevated IL-27 associates with disease progression in hepatocellular carcinoma (HCC). Recent translational advances include IL-27-expressing viral vectors, dendritic cell platforms, and IL-27-blocking antibodies, underscoring its therapeutic duality. Overall, IL-27 functions as a context-dependent cytokine whose final effect on tumor progression is determined by the intrinsic characteristics of each tumor, the composition of tumor microenvironment (TME) and the interaction between immune and epithelial cells. Understanding the mechanisms that drive the dual roles of IL-27 across different GI cancers will be important for designing rational immunotherapeutic strategies that either enhance or inhibit IL-27 activity.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153214"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exogenous recombinant complement proteins C3a and C5a regulate osteogenic differentiation of P-PDLSCs: a process associated with the Wnt/beta-catenin axis","authors":"Lingyan Peng,&nbsp;Yong Zhang,&nbsp;Xiaohui Yin,&nbsp;Fei Li,&nbsp;Jing Qiao","doi":"10.1016/j.imbio.2026.153218","DOIUrl":"10.1016/j.imbio.2026.153218","url":null,"abstract":"<div><h3>Objective</h3><div>Concentrated growth factor (CGF) is rich in growth factors and complement proteins like C3a and C5a, showing promise for enhancing tissue regeneration. This study explores the regulatory effects of recombinant C3a/C5a proteins on the osteogenic differentiation of PDLSCs in an inflammatory microenvironment and their potential association with the Wnt/β-catenin pathway.</div></div><div><h3>Methods</h3><div>P-PDLSCs were generated by treating PDLSCs with IL-1β (5 ng/mL) and TNF-α (10 ng/mL) for 24 h. Subsequently, P-PDLSCs were treated with C5a and C3a, followed by evaluation of cell viability and early osteogenic differentiation capacity (ALP activity). To investigate the underlying mechanism, cells were treated with the Wnt/β-catenin pathway inhibitor, XAV939, either alone or combined with C3a/C5a. Cell viability, ALP activity, and the mRNA and protein levels of AKT, Runx2, and β-catenin were measured.</div></div><div><h3>Results</h3><div>Compared with the control group, exogenous recombinant C3a and C5a treatment can promote the proliferation and early osteogenic differentiation of P-PDLSCs. Additionally, through KEGG enrichment, the Wnt/β-catenin pathway was identified as a key target. The pro-osteogenic effects of C3a/C5a were partially reversed by XAV939, pointing to a potential correlation with the Wnt/β-catenin signaling pathway.</div></div><div><h3>Conclusion</h3><div>Exogenous recombinant C3a/C5a is associated with increased early osteogenic differentiation of P-PDLSCs, a process correlated with the activation of the Wnt/β-catenin signaling pathway, providing potential insights into regenerative strategies for periodontal tissues.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153218"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Bulk and Single-Cell RNA Sequencing to Identify Prognostic Genes Associated with Adaptive Immunity and the Tumor Microenvironment in Cholangiocarcinoma for Risk Model Construction","authors":"Wang Jie,&nbsp;Zhou Jixiang,&nbsp;Bao Yang,&nbsp;Wang Yanting,&nbsp;Liu Ling","doi":"10.1016/j.imbio.2026.153213","DOIUrl":"10.1016/j.imbio.2026.153213","url":null,"abstract":"<div><h3>Background</h3><div>Cholangiocarcinoma (CCA) has a complex tumor microenvironment (TME) and poor immunotherapy response. Understanding how the adaptive immune response (AIR) affects the TME and prognosis is critical.</div></div><div><h3>Methods</h3><div>All data were obtained from publicly available resources. Differentially expressed genes (DEGs) were identified by comparing tumor vs. normal and stromal/immune score-based samples, and were then intersected with an AIR gene set to obtain candidate genes. Prognostic genes identified by univariate Cox regression were used to build a risk model. Analyses included functional enrichment, immune landscape, drug sensitivity, and single-cell RNA sequencing (scRNA-seq) to identify key cell types, cell–cell communication, and pseudotime trajectories.</div></div><div><h3>Results</h3><div>Intersection analysis yielded 68 candidate genes, from which eight prognostic genes (C1QA, CD55, ZAP70, CLEC4M, FCAMR, LILRA1, CD80, C17orf99) were identified. The risk model stratified patients into high-risk (HRG) and low-risk (LRG) groups with significantly different overall survival. LRG was enriched for immune activation pathways, whereas HRG exhibited an immune-excluded phenotype (lower CD8+ T cell infiltration, higher exclusion score). LRG showed higher sensitivity to gemcitabine and ABT-737. Macrophages were identified as key cells, with enhanced malignant cell–macrophage communication via the MIF–(CD74 + CXCR4) axis in CCA. Macrophages comprised seven heterogeneous subtypes and five distinct differentiation states. Firmicutes abundance was lower in the HRG. A nomogram integrating risk score and Firmicutes demonstrated favorable predictive performance.</div></div><div><h3>Conclusion</h3><div>An AIR-related gene signature stratifies CCA prognosis by reflecting TME composition rather than tumor-intrinsic drivers, highlighting immune cell–centric mechanisms and intratumoral microbiota. The nomogram may aid prognostic stratification in research settings.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153213"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial-cellular resolution analysis of ferroptosis-associated immune microenvironment heterogeneity in osteoarthritic cartilage","authors":"Zhiwen Zheng,&nbsp;Junjie Wang,&nbsp;Bin Dai,&nbsp;Jiafeng Peng,&nbsp;Hongmei Cai,&nbsp;Zheng Gong,&nbsp;Hongxing Zhang,&nbsp;Junchen Zhu","doi":"10.1016/j.imbio.2026.153212","DOIUrl":"10.1016/j.imbio.2026.153212","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage destruction, in which dysregulated cell death and immune microenvironment remodeling play critical roles. Ferroptosis, an iron-dependent form of regulated cell death, has recently been implicated in OA pathogenesis; however, its role in modulating immune responses remains poorly understood. This study aimed to elucidate the interplay between ferroptosis and the immune microenvironment in osteoarthritic cartilage, with a particular focus on the potential association between ferroptosis and macrophage polarization. Bulk transcriptomic analysis was performed to identify ferroptosis-related genes, followed by least absolute shrinkage and selection operator regression to screen key biomarkers. Integrated single-cell and spatial transcriptomic analyses were used to characterize ferroptotic chondrocytes and their spatial association with immune cells. Gene co-expression and functional enrichment analyses identified a ferroptosis-associated core module enriched in pathways related to ferroptosis, inflammatory responses, and oxidative metabolism. Immune infiltration analysis revealed a significant positive correlation between module hub genes and macrophage infiltration, particularly pro-inflammatory macrophages. Spatial transcriptomics further demonstrated marked colocalization between high-ferroptosis chondrocytes and macrophage-enriched regions. Cell–cell communication analysis highlighted the SPP1 signaling pathway as a potential mediator of communication between ferroptotic chondrocytes and macrophages. Mechanistic and in vitro experiments further suggested that ferroptotic chondrocytes may contribute to macrophage polarization toward a pro-inflammatory phenotype, potentially through the SPP1 signaling axis. Collectively, these findings suggest a potential molecular link between ferroptosis and immune inflammation in OA and identify the SPP1–ferroptosis axis as a promising therapeutic target for OA intervention.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153212"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential correlation assessment identified by a genome-wide association study using induced pluripotent stem cells from patients with IgAN","authors":"Akira Mima,&nbsp;Hirofumi Morihara","doi":"10.1016/j.imbio.2026.153203","DOIUrl":"10.1016/j.imbio.2026.153203","url":null,"abstract":"<div><div>It is unclear whether genetic mutations associated with inflammation and mitochondrial function are involved in the progression and exacerbation of immunoglobulin A nephropathy (IgAN). In this study, we aimed to investigate the IgAN genetic background.</div><div>Genome-wide association studies (GWAS) were performed using four lines of human-induced pluripotent stem cells (hiPSCs) established from two patients with IgAN, possible IgAN, and minimal change disease.</div><div>There were 4641 single nucleotide polymorphisms (SNPs) in hiPSCs derived from patients with IgAN or possible IgAN compared to those in hiPSCs derived from minimal change disease as a control. We identified genes expressed more frequently than those in hiPSCs derived from minimal change disease. We identified SNP-inhibited genes that were significantly associated with inflammation (115 SNPs), oxidative stress (29 SNPs), fibrosis (10 SNPs), and mitochondrial function (158 SNPs).</div><div>Our GWAS, using hiPSCs derived from patients with IgAN or possible IgAN, indicated that these mutations may be linked to mitochondrial dysfunction, inflammation, and extracellular matrix production.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153203"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 a prognostic two-lncRNA panel correlated with immune-associated transcripts for forecasting overall survival in pancreatic cancer","authors":"Hajar Eftekhari,&nbsp;Arash Safarzadeh,&nbsp;Emad Babakhanzadeh,&nbsp;Soudeh Ghafouri-Fard","doi":"10.1016/j.imbio.2026.153221","DOIUrl":"10.1016/j.imbio.2026.153221","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic cancer is among the most lethal cancers because of late diagnosis and inadequate therapeutic preferences. The tumor microenvironment and immune response have critical roles in disease progression and patient outcomes. LncRNAs are regulators of immune function and tumorigenesis, yet their prognostic value in pancreatic cancer remains partly clarified.</div></div><div><h3>Methods</h3><div>RNA-sequencing data and corresponding clinical features for 178 pancreatic cancer patients were obtained from TCGA. Immune-related mRNAs were retrieved from the MSigDB, and immune-related lncRNAs were identified based on a significant Pearson correlation with at least two immune-related mRNAs. Regression analyses were sequentially applied to construct a prognostic immune-related lncRNA set. The predictive performance of the set was assessed using time-dependent ROC curves and Kaplan-Meier survival analysis in both the TCGA training cohort and an independent external validation cohort (GSE224564).</div></div><div><h3>Results</h3><div>From 4059 lncRNAs, 1172 immune-related lncRNAs demonstrated strong associations with immune-related mRNAs. Sequential screening identified 34 survival-associated lncRNAs by univariate Cox regression (<em>P</em> &lt; 0.01), 12 lncRNAs following LASSO regression, and ultimately two lncRNAs—CASC8 (HR = 1.7, <em>P</em> &lt; 0.05) and LINC01004 (HR = 0.54, P &lt; 0.05)—by multivariate Cox regression. A risk score signature was developed using these two lncRNAs. Time-dependent ROC analysis demonstrated moderate-to-good predictive precision in the training cohort, with area under the curve (AUC) values of 0.702, 0.774, and 0.84 for 1-, 3-, and 5-year overall survival, respectively. Patients in the high-risk group exhibited significantly worse survival compared to the low-risk group (<em>P</em> &lt; 0.05). External validation in the GSE224564 cohort confirmed consistent risk stratification (<em>P</em> = 0.019), though with lower discriminative accuracy (AUC ∼ 0.60). Multivariate analysis demonstrated that the risk score acted as an independent prognostic factor in both cohorts.</div></div><div><h3>Conclusion</h3><div>The CASC8 and LINC01004 immune-related lncRNA profile serves as a potential prognostic marker for pancreatic cancer. This set demonstrates increasing predictive trends over time in the training dataset. The presented findings offer novel insights into the correlation of immune-related lncRNAs with pancreatic cancer progression and provide a foundation for future risk stratification modeling.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153221"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and structural characterization of soluble dectin-1 with β-glucan-binding activity in THP-1 cell culture supernatant","authors":"Naoki Arima,&nbsp;Rui Tada,&nbsp;Ken-ichi Ishibashi,&nbsp;Takashi Kanno,&nbsp;Daisuke Yamanaka,&nbsp;Yoshiyuki Adachi","doi":"10.1016/j.imbio.2026.153175","DOIUrl":"10.1016/j.imbio.2026.153175","url":null,"abstract":"<div><div>Dectin-1, a major receptor in antifungal immunity, functions as membrane-bound Dectin-1 (mDectin-1). However, the biological functions of its soluble form, sDectin-1, remain poorly understood. In this study, we established a THP-1 cell line stably expressing human Dectin-1 A with N-terminal FLAG and C-terminal HiBiT tags to analyze the mechanism underlying the presence of sDectin-1 in the extracellular environment, its molecular form, and its capabilities. As a result, sDectin-1 was detected constitutively in the culture supernatant, but its level increased upon stimulation via the Dectin-1–Syk pathway (curdlan) and by Dectin-1-independent inflammatory signals (TNF-α). Functional analysis revealed that sDectin-1 retains its ligand-binding capacity to both insoluble and soluble β-glucans. Furthermore, western blotting suggested that the predominant molecular form of sDectin-1 is an N-terminally truncated fragment, consistent with the extracellular domain truncation. This study demonstrates that sDectin-1 is a functional, soluble receptor that retains ligand-binding capacity and whose level is regulated by inflammatory signals. This finding suggests that sDectin-1 may function as a decoy receptor or trans-signaling factor, providing new perspectives on antifungal immunity.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153175"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring therapeutic targets for neuroinflammation in sepsis-associated encephalopathy: a combined network pharmacology and bioinformatics approach","authors":"Huijie Shen,&nbsp;Xuecheng Wei","doi":"10.1016/j.imbio.2026.153208","DOIUrl":"10.1016/j.imbio.2026.153208","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-associated encephalopathy (SAE) is a frequent but underrecognized complication of sepsis, yet no effective pharmacological interventions are currently available. Traditional Chinese medicine (TCM) offers a promising multi-component and multi-target strategy.</div></div><div><h3>Methods</h3><div>We used an integrative strategy combining network pharmacology, bioinformatics, and molecular modeling was employed to investigate a seven-herb TCM formula. Active compounds were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and disease-related genes were obtained from GSE135838. Overlapping targets were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) analyses, and network topology analysis was performed to identify key hub genes and core compounds. Compound–target interactions were evaluated using molecular docking, molecular dynamics (MD) simulation, and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) analysis.</div></div><div><h3>Results</h3><div>A total of 121 active compounds and 255 targets were identified, with 29 overlapping genes related to SAE. Five hub genes—amyloid precursor protein (APP), B-cell lymphoma 2 (BCL2), caspase-3 (CASP3), intercellular adhesion molecule 1 (ICAM1), and interleukin-6 (IL-6)—and five core compounds (quercetin, luteolin, kaempferol, β-sitosterol, and 7-<em>O</em>-methylisomucronulatol) were identified. Molecular docking revealed favorable compound–target interactions (binding energies: −5.7 to −9.1 kcal/mol). MD simulations confirmed stable APP–ligand complexes throughout the 100 ns simulation period. MM-PBSA analysis showed that β-sitosterol exhibited the strongest binding affinity toward APP (ΔGbind = −23.67 kcal/mol).</div></div><div><h3>Conclusion</h3><div>This study highlights the multi-target and multi-pathway therapeutic potential of a seven-herb TCM formula against SAE and identifies potential bioactive compounds and therapeutic targets for further investigation.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153208"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil-to-HDL-C ratio and systemic inflammation response index are associated with the risk of abdominal aortic aneurysm","authors":"Junqi Peng,&nbsp;Dengwei Cao,&nbsp;Yun Wu,&nbsp;Hanqing Zhang,&nbsp;Lushun Yuan,&nbsp;Jinping Liu,&nbsp;Song Chen","doi":"10.1016/j.imbio.2026.153217","DOIUrl":"10.1016/j.imbio.2026.153217","url":null,"abstract":"<div><div>Abdominal aortic aneurysm (AAA) is characterized by an inflammatory response that plays a crucial role in its pathogenesis. This study aimed to investigate the association between novel circulating inflammatory biomarkers and AAA. A total of 579 patients (240 with AAA and 339 with valvular heart disease as non-AAA controls) were enrolled from the Department of Cardiovascular Surgery at Zhongnan Hospital of Wuhan University between January 2020 and October 2024. Clinical characteristics and levels of circulating inflammatory markers were compared between the two groups. Multivariate logistic regression analyses indicated that male gender, lower HDL<img>C, and higher neutrophil-to-HDL-C ratio (NHR), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were independent but modest risk factors for AAA (<em>P</em> &lt; 0.05). Furthermore, these biomarkers correlated with AAA severity. In conclusion, gender, HDL<img>C, NHR, SIRI, and AISI serve as useful predictive factors for AAA. The nomogram prediction model demonstrated good discriminatory ability and may facilitate early diagnosis of AAA.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 4","pages":"Article 153217"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-abundance plasma proteomics reveals NET-associated molecular signatures in rheumatoid arthritis","authors":"Feng Zhu ,&nbsp;Wei Zhang ,&nbsp;Xuejia Zheng ,&nbsp;Dongzhou Liu ,&nbsp;Zhipeng Zeng ,&nbsp;Huihui Tao ,&nbsp;Yujie Zhang ,&nbsp;Tianyuan Li ,&nbsp;Yurong Qin ,&nbsp;Donge Tang ,&nbsp;Yong Dai","doi":"10.1016/j.imbio.2026.153188","DOIUrl":"10.1016/j.imbio.2026.153188","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation and multi-organ involvement, yet its molecular mechanisms remain incompletely understood. While plasma proteomics provides valuable insights into disease-associated alterations, most studies focus on high-abundance proteins. Low-abundance plasma proteins, which often serve as critical regulators of immune signaling and inflammatory pathways, remain insufficiently characterized in RA.</div></div><div><h3>Methods</h3><div>Plasma samples from 27 RA patients and 10 healthy controls (HCs) were analyzed using the SomaScan P11K platform. Differential expression analysis, pathway enrichment, protein-protein interaction network construction, and drug repurposing analyses were performed. Enzyme-linked immunosorbent assay (ELISA) validation was conducted in independent cohorts.</div></div><div><h3>Results</h3><div>A total of 218 differentially expressed low-abundance proteins were identified. Neutrophil extracellular trap (NET) formation was the most significantly enriched KEGG pathway (<em>p</em> = 0.0057), with seven NET-associated proteins showing differential expression. Protein-protein interaction (PPI) analysis revealed functional integration with mitogen-activated protein kinase (MAPK) and chemokine signaling pathways. ELISA validation confirmed differential expression of NCF1, PPIF, and HDAC3. Drug repurposing analysis identified several candidate compounds, among which Delsemidine emerged as one of the top-ranked compounds in the exploratory analysis.</div></div><div><h3>Conclusions</h3><div>This study systematically characterizes NET-associated molecular signatures in the low-abundance plasma proteome of RA and provides a hypothesis-generating basis for future validation of candidate biomarkers and related pathways.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153188"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948097","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}