Search Results (205)

Background/Objectives: CLEC-2 (C-type lectin-like receptor 2), the newest discovered platelet receptor, is involved in platelet activation and aggregation, the inflammatory response, tumor growth, metastasis, and angiogenesis. These unique features make CLEC-2 a promising candidate for a new biomarker and therapeutic target. The aim of our study was to evaluate the diagnostic value of CLEC-2 in patients with colorectal cancer (CRC). Methods: The serum CLEC-2 concentration was determined using ELISA methods in 64 CRC patients and 25 healthy subjects. Results: Our results indicate that the concentration of the serum CLEC-2 was significantly higher in CRC patients than in healthy subjects. Furthermore, the CLEC-2 levels were significantly higher in G3- than G2-grade CRC, and in patients with more advanced CRC, such as those with lymph node and distant metastases, than in patients without any metastases. CLEC-2 showed a positive correlation with platelet indices (PLT and MPV). The area under the ROC curve confirmed CLEC-2’s excellent diagnostic power in distinguishing between patients with CRC. Conclusions: Our results indicate that CLEC-2 may be associated with CRC development and suggest that the identification of this biomarker could be useful for determining CRC progression. Full article

In glioblastoma, the strong immunosuppression of the tumor immune microenvironment fosters tumor aggressiveness and decreases the effectiveness of therapeutic interventions, including immunotherapies. An intricate network of connections among tumor cells, stroma and infiltrating immune cells sustains immunosuppression. Lectins are immunoregulatory glycan-binding receptors contributing to immunosuppression. Their targeting is proposed as an appealing strategy for anti-cancer therapy. In this work, network-based approaches were exploited to identify a lectin profile that could dissect the complexity of tumor-immunity interactions in glioblastoma. Differential co-expression analysis, employing TCGA, CGGA and GTEx databases (145, 133 and 255 samples, respectively), identified a cluster of novel C-type lectins, with ASGR2 and CLEC12A as principal hubs. Furthermore, TIMER2.0 analysis revealed that their expression was significantly associated with immunosuppressive cells. ASGR2 and CLEC12A expression was also validated by cytofluorimetric analysis on both tumor and liquid biopsies from 20 glioblastoma patients. We report that ASGR2 and CLEC12A C-type lectins are associated with tumor-infiltrating immunosuppressive myeloid subsets and discriminate patients’ poor prognosis. These results suggest that C-type lectins may contribute to the immunosuppressive network sustained by infiltrating myeloid immune cells in GB, resulting in exploitable targets for therapeutic interventions. Full article

Complement and pathogenic antibodies act independently and together to mediate the pathology of many autoimmune diseases. To address these drivers of disease, we generated a monoclonal antibody (mAb), CSL305, that binds and inhibits both complement and the neonatal Fc (fragment crystallizable) receptor FcRn. The fragment antigen binding (Fab) portion of CSL305 was engineered to bind both human C2 (huC2) zymogen and the active fragment huC2b to inhibit the classical and lectin complement pathways in vitro, and C3b deposition on primary lung endothelial cells using a 3-dimensional microvascular model system. Engineering of a triple amino acid mutation (“YPY” motif) into the Fc region of CSL305 increased its affinity to FcRn at both acidic and neutral pH, allowing it to also act as a potent FcRn antagonist. Intracellular trafficking experiments demonstrated that CSL305, but not the wild-type (WT) mAb lacking the YPY motif, was able to block immunoglobulin G (IgG) recycling in vitro. The generation of a high resolution 2.6Å crystal structure of CSL305 Fab region bound to huC2b showed that the epitope lies directly over the huC2b catalytic triad, providing evidence of its complement mechanism of action as a neutralising mAb. Early pharmacokinetic (PK)/pharmacodynamic (PD) studies using CSL305 in cynomolgus monkeys demonstrated both complement inhibition and FcRn antagonism in vivo, with reductions in complement classical pathway activity and endogenous IgG observed following single intravenous (IV) administration. CSL305 thus represents a dual-functional mAb as a potential therapeutic candidate. Full article

The spotted knifejaw (Oplegnathus punctatus) has emerged as a species with substantial potential for aquaculture development in China. However, its industrial cultivation is severely constrained by viral diseases. Among these, viral nervous necrosis (VNN), caused by nervous necrosis virus (NNV), represents a critical bottleneck to the sustainable development of this industry. In order to elucidate the immune response mechanisms of the brain cells of spotted knifejaw, this study established a poly (I:C) stimulation model in vitro and performed transcriptomic sequencing to analyze the differentially expressed genes (DEGs) after stimulation. There were 3169, 3228, and 3262 DEGs at 3 h, 6 h, and 12 h compared to 0 h (control), respectively. Co-expression time clustering of DEGs identified two gene clusters (cluster 6 and cluster 10), which included several immune-related genes. GO and KEGG enrichment analyses indicated that DEGs among the four time points were significantly enriched in immune signaling pathways, including the NOD-like receptor, RIG-I-like receptor, C-type lectin receptor, and Toll-like receptor pathways, as well as disease-response pathways. In total, 1398 common DEGs were identified among three comparative groups, which delineated six interaction clusters and 30 hub genes in protein–protein interaction (PPI) network analysis. By integrating a cellular model with transcriptomics, this study provides preliminary insights into the molecular immune mechanisms underlying the response of brain cells to poly (I:C) stimulation, offering important theoretical support for future research on disease-resistant breeding and disease control strategies in spotted knifejaw. Full article

The balance of alveolar macrophage (AM) polarization is severely disrupted in chronic inflammatory diseases like bronchiectasis, where a persistent pro-inflammatory (M1) phenotype perpetuates inflammation. To address this, we developed a high-throughput platform using a series of synthetic glycoligands (L1-L5) on a polyethyleneimine (PEI) scaffold. These ligands, which have varying affinities for macrophage lectin-like receptors, were used for phenotypic “fingerprinting” of AM subpopulations from pediatric bronchiectasis patients and a healthy control. Analysis of bronchoalveolar lavage fluid (BALF) revealed a pathogenic, M1-dominant profile (55% M1) in patients, confirming a state of chronic inflammation, which starkly contrasted with the quiescent, M0-dominant profile in the healthy control. We then leveraged this platform for targeted immunomodulation, using a drug-ligand conjugate to steer the dysregulated macrophage population toward a healthy state. The most potent conjugate, Dox-L5, dramatically suppressed the pathogenic M1 population (from 55% to 16%). This M1 suppression was accompanied by a significant shift toward the M2a (tissue-repair) phenotype and the emergence of a quiescent M0-like population, effectively remodeling the AM profile. This work validates a glycan-based platform for both diagnosing and correcting pathological macrophage imbalances. Our targeted approach offers a precise strategy to resolve chronic inflammation in bronchiectasis by suppressing M1 macrophages and promoting a pro-resolving M0/M2 phenotype, thereby restoring lung homeostasis. Full article

Acne vulgaris is a prevalent chronic inflammatory skin disorder affecting over 85% of adolescents. Emerging evidence indicates that Cutibacterium acnes phylotype IA₁ contributes to acne initiation and progression, yet its precise mechanisms in epidermal keratinocytes remain unclear. This study investigated C. acnes IA1’s effects on keratinocyte behavior using an in vitro HaCaT cell model. Cells were co-cultured with live C. acnes IA₁ (CICC 10864) for 24 h. Transcriptomic profiling identified 769 differentially expressed genes (DEGs; adjusted p < 0.05, |log2FC| > 1), including 392 upregulated and 377 downregulated. The protein–protein interaction network analysis via Cytoscape revealed key hub genes (HNRNPA2B1, HNRNPM, RBM39). Enrichment analyses (GO, KEGG, Reactome, DO) highlighted significant involvement of the C-type lectin receptor (CLR) signaling pathway. Validation experiments showed cellular morphological changes, altered structure, and markedly elevated interleukin-6 (IL-6; p < 0.01), underscoring its role in inflammation. These findings suggest C. acnes IA₁ drives acne pathogenesis by regulating hub genes that influence sebaceous gland inflammation, immune activity, and keratinocyte proliferation, positioning them as potential biomarkers for microbiome-targeted therapies. Limitations include the in vitro model’s lack of in vivo skin microenvironment complexity and use of only one representative IA₁ strain. Full article

C-type lectins (CTLs) are a large family of calcium-dependent carbohydrate-binding proteins that play crucial roles in innate immunity as pattern recognition receptors. Bivalve mollusks possess exceptionally diverse and expanded repertoires of CTLs, yet a systematic review integrating their structural, functional, and regulatory aspects has been lacking. This article provides a comprehensive synthesis of current knowledge on bivalve CTLs, analyzing their biosynthesis, complex tissue-specific expression under both normal and stressed conditions, and their multifaceted roles in immune defense and other physiological processes. Our analysis consolidates data on their diverse domain architectures, phylogenetic relationships, and the variability of key motifs within their carbohydrate-recognition domains. The results demonstrate that bivalve CTLs are not only critical for pathogen recognition, agglutination, and phagocytosis but also involved in processes like nutrition, development, byssus formation and biomineralization. However, a significant finding is that the detailed carbohydrate specificity for most bivalve CTLs remains poorly characterized, often limited to monosaccharide inhibition assays. In conclusion, while the immune role of bivalve CTLs is well-established, this review underscores a critical gap in understanding their fine glycan-binding profiles. Therefore, a shift in the focus of future research towards elucidating their structure and carbohydrate specificity is required for a full understanding of their biological functions and an assessment of their biomedical potential. Full article

In olive flounder (Paralichthys olivaceus) suffering from emaciation disease, the intestinal myxozoan Enteromyxum leei is considered a major causative agent. This disease causes severe economic losses in East Asian aquaculture, and even though the pathological outcomes have been well described, the molecular mechanisms underlying host immune imbalance are unclear. We performed RNA sequencing of posterior intestinal tissue from infected and control fish, yielding high-quality datasets and 2666 differentially expressed genes (1589 downregulated, 1077 upregulated). Enrichment analyses revealed a significant modulation of immune processes, particularly cytokine activity, chemokine signaling, apoptosis regulation, and lymphocyte trafficking. Kyoto Encyclopedia of Genes and Genomes analysis identified six immune-related pathways that were the most affected: Toll-like receptor, NOD-like receptor, intestinal immune network for IgA production, C-type lectin receptor, RIG-I-like receptor, and cytosolic DNA sensing. Network mapping highlighted nine hub genes, including cxcl8a, pik3r1, mapk10, and itpr1b, which were shared across multiple pathways and validated by qRT-PCR. Our results demonstrate that E. leei disrupts intestinal immune homeostasis by suppressing chemokine-driven inflammation and adaptive responses while simultaneously enhancing nucleic acid-sensing and stress pathways. This dual modulation provides new insights into the intestinal immune dysregulation underlying enteromyxosis and establishes a molecular basis for future diagnostic and preventive strategies in olive flounder aquaculture. Full article

Shewanella putrefaciens is a significant bacterial pathogen causing high mortality in farmed largemouth bass (Micropterus salmoides). This study investigated the molecular immune responses in its primary target organs, the liver and spleen, via transcriptomic profiling at 24 h post-infection. We identified 458 significantly differentially expressed genes (DEGs) in the liver and 1405 in the spleen. Gene Ontology enrichment analysis revealed organ-specific immune strategies: the liver response was characterized by type I interferon signaling pathway, whereas the spleen response centered on the regulation of innate immune response. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that fatty acid metabolism and cytokine-cytokine receptor interaction were significantly enriched in the liver. In contrast, the C-type lectin receptor signaling pathway and cytokine-cytokine receptor interaction were the most prominent in the spleen. Several key DEGs (e.g., stat1a, rsad2, pglyrp5, pglyrp6, acaca, stat2, lepb) associated with immune response, metabolic adaptation, and cellular stress were identified, suggesting a coordinated host mechanism involving pathogen recognition, immunomodulation, and tissue repair. These results provide crucial insights into the immunomodulatory processes in largemouth bass against S. putrefaciens infection. Full article

Background: Hypospadias is often associated with abnormal prepuce development. Investigating the differences between the inner prepuce of hypospadias patients and normal controls at the transcriptomic level and histological characteristics helps to reveal the causes of its developmental abnormalities or implement targeted treatments. Materials and Methods: Dorsal and ventral inner preputial tissues were collected from 31 hypospadias patients and 21 phimosis children (controls). Differences in gene expression between the two groups were studied via transcriptomic sequencing and enrichment analysis. Corresponding histological features were further validated by histological staining. Results: Transcriptomic sequencing results showed that, compared to the control group, the dorsal inner prepuce of the hypospadias group had 97 upregulated and 10 downregulated genes; the ventral prepuce had 140 upregulated and 99 downregulated genes. Among all upregulated genes, 44 were closely related to fibrosis. Other significantly enriched terms included cornified envelope formation, efferocytosis, C-type lectin receptor signaling pathway, and complement and coagulation cascades. Histological validation revealed that the dorsal inner prepuce of hypospadias children contained more collagen fibers, a higher ratio of type I/III collagen, and lower microvessel density, showing some correlation with the severity of hypospadias. Conclusions: This study demonstrated a hyper-fibrotic state in the inner prepuce of hypospadias, which may significantly impact post-operative wound healing and complications. Full article

Vaccine adjuvants play a crucial role in the field of vaccinology, yet they remain one of the least developed and poorly characterized components of modern biomedical research. The limited availability of clinically approved adjuvants highlights the urgent need for new molecules with well-defined mechanisms and improved safety profiles. Hemocyanins, large copper-containing metalloglycoproteins found in mollusks, represent a unique class of natural immunomodulators. Hemocyanins serve as carrier proteins that help generate antibodies against peptides and hapten molecules. They also function as non-specific protein-based adjuvants (PBAs) in both experimental human and veterinary vaccines. Their mannose-rich N-glycans allow for multivalent binding to innate immune receptors, including C-type lectin receptors (e.g., MR, DC-SIGN) and Toll-like receptor 4 (TLR4), thereby activating both MyD88- and TRIF-dependent signaling pathways. Hemocyanins consistently favor Th1-skewed immune responses, which is a key characteristic of their adjuvant potential. Remarkably, their conformational stability supports slow intracellular degradation and facilitates dual routing through MHC-II and MHC-I pathways, thereby enhancing both CD4+ and CD8+ T-cell responses. Several hemocyanins are currently being utilized in biomedical research, including Keyhole limpet hemocyanin (KLH) from Megathura crenulata, along with those from other gastropods such as Concholepas concholepas (CCH), Fissurella latimarginata (FLH), Rapana venosa (RvH), and Helix pomatia (HpH), all of which display strong immunomodulatory properties, making them promising candidates as adjuvants for next-generation vaccines against infectious diseases and therapeutic immunotherapies for cancer. However, their structural complexity has posed challenges for their recombinant production, thus limiting their availability from natural sources. This reliance introduces variability, scalability issues, and challenges related to regulatory compliance. Future research should focus on defining the hemocyanin immunopeptidome and isolating minimal peptides that retain their adjuvant activity. Harnessing advances in structural biology, immunology, and machine learning will be critical in transforming hemocyanins into safe, reproducible, and versatile immunomodulators. This review highlights recent progress in understanding how hemocyanins modulate mammalian immunity through their unique structural features and highlights their potential implications as potent PBAs for vaccine development and other biomedical applications. By addressing the urgent need for novel immunostimulatory platforms, hemocyanins could significantly advance vaccine design and immunotherapy approaches. Full article

Background: As the member of the B7 family, V-set and immunoglobulin domain-containing 4 (VSIG4) plays an essential role in regulating immune responses against bacterial infection, autoimmune disease, and chronic viral infection. However, the role of VSIG4 in acute viral infections remains largely unclear. Methods: Here, we constructed a gene-targeted VSIG4-deficient mouse model and then infected it with influenza to explore the detailed VSIG4-involved mechanism. Results: Our results demonstrated that the gene-deficient mice exhibited reduced survival rates, ranging from 25% to 50%, after being infected with different influenza virus strains. At the sites of infection, an increased number of CD8⁺ T cells, along with heightened expression of pro-inflammatory cytokines, e.g., Il-6 and TNFα, may have contributed to tissue damage. The recombinant VSIG4 protein slightly improved protection from the influenza challenge, suggesting regulatory functions of VSIG4 during infection. Using in vitro cell models, we show that the type C lectin receptor pathway member DC-SIGNR1 (CD209) is an essential factor during acute virus infection. The affinity and CO-IP tests indicated an interaction between CD209 and VSIG4, but not through protein modification. Conclusions: Therefore, VSIG4 functionally protected mice by regulating the type C lectin receptor pathway to inhibit excessive Th1 immune responses and inflammation. Our findings highlight the importance of considering immune homeostasis in the development of therapies for severe infections. Full article

Gliomas present as highly heterogeneous and aggressive central nervous system (CNS) tumors with challenging diagnosis and management. Traditional and current therapies are lacking efficacy in overcoming the complex and dynamic behavior of gliomas and the local tumor microenvironment. Emerging research highlights the significant role of innate immune receptors including Toll-like, NOD-like and RIG-like receptors, as well as cGAS-STING receptors, scavenger and C-type lectin receptors in glioma development and progression. These receptors can both impact immune modulation as well as facilitate tumor growth through interactions with tumor-associated macrophages, myeloid-derived suppressor cells and cytokine networks, contributing to immune evasion in the tumor microenvironment. Herein, we discuss the main signaling pathways induced through innate immune receptors in gliomas along with their functional properties in glioma pathology while exploring current applications to treatment. Utilizing innate immune receptors as therapeutic targets holds great promise, especially when used along with traditional chemotherapy and radiation schemes, strengthening immune responses. Future studies focusing on the deeper understanding of innate immune receptors signaling and complexity are highly required to enable novel immunoregulatory treatment schemes for gliomas. Full article

Bovine mastitis is one of the most prevalent and economically significant diseases affecting dairy cows worldwide, with Escherichia coli (E. coli) recognized as one of the principal pathogens causing acute mastitis. The innate immune system plays a crucial role in the defense of the bovine mammary gland, serving as the first line of defense against pathogen invasion. This study elucidated the pathological mechanisms and immune response-related molecular regulatory networks involved in E. coli-induced bovine mastitis. Histopathological and apoptosis analyses of mammary tissues were performed using hematoxylin-eosin (HE) staining and TUNEL staining, respectively, while RNA sequencing (RNA-seq) was conducted to identify differentially expressed genes (DEGs) and their associated signaling pathways. HE staining revealed typical inflammatory lesions in the mammary glands of mastitis cows. TUNEL staining further confirmed that the level of apoptosis in the mastitis group was significantly higher than in the healthy control group (p < 0.0001). RNA-seq analysis identified 2717 DEGs, with 2238 upregulated and 479 downregulated genes. The top 20 significantly upregulated genes (e.g., S100A12, IL1RN, IL1R2, CXCL8, SAA3, S100A8, S100A9, TREML2, TREM1, M-SAA3.2, PTX3, MMP9) were predominantly involved in inflammatory immune regulation, acute phase responses (e.g., HP, SAA3), and cellular signal transduction (e.g., PLEK, LPAR3). Gene Ontology (GO) enrichment analysis revealed that these DEGs were mainly associated with biological processes, such as signal transduction, immune response, inflammatory response, and transcriptional regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these DEGs were significantly enriched in key inflammatory and immune regulatory pathways, including the TNF signaling pathway, C-type lectin receptor signaling pathway, Chemokine signaling pathway, NOD-like receptor signaling pathway, NF-κ B signaling pathway, and IL-17 signaling pathway, suggesting that these pathways play central roles in the mammary immune defense against E. coli infection. In conclusion, this study demonstrated at the histopathological, cellular apoptosis, and transcriptomic levels that E. coli infection induces mammary tissue damage and apoptosis by activating immune and inflammation-related genes (S100A12, IL1RN, IL1R2, CXCL8, SAA3, S100A8, S100A9, TREML2, TREM1, M-SAA3.2, PTX3, MMP9) and key signaling pathways (TNF signaling pathway, C-type lectin receptor signaling pathway, Chemokine signaling pathway, NOD-like receptor signaling pathway, NF-κ B signaling pathway, IL-17 signaling pathway). The findings of this study provide a theoretical basis for probing into the pathogenesis of bovine mastitis and the development of targeted interventions. Full article

The American cockroach (Periplaneta americana) serves as an exemplary model for regeneration research due to its exceptional regenerative capabilities, particularly in appendage regeneration. In this study, regenerated coxa tissue underwent histological analysis through H & E straining. Microscopic examination revealed the progression of regeneration. To elucidate the underlying mechanisms, a comparative transcriptomic analysis was conducted between regenerating legs and non-amputated control legs. This analysis identified 2343 differentially expressed genes (DEGs) between 0 days post-amputation (0 dpa) and 7 dpa, 2963 DEGs between 14 dpa and 0 dpa, and 3135 DEGs between 14 dpa and 7 dpa. Significantly, several DEGs are associated with growth- or regeneration-related processes, including extracellular matrix (different collagen, Pro-resilin isoforms, integrin beta (itgb) and matrix metalloproteinase (mmp)), immune-related genes (Toll-like receptor 13 (tlr13), defensin (def), drosomycin-like defensin (dld), Polyphenoloxidases2 (ppo2), cytochrome P450 (p450), peptidoglycan recognition protein (pgrp) and secreted C-type lectin (sClec)), insulin-like growth factor (IGF) and Epidermal Growth Factor Receptor (EGFR). Functional validation through RNA interference (RNAi) further suggested that EGFR and a specific C-type lectin (Regenectin) regulate leg regeneration in Periplaneta americana. These findings enhance our understanding of the molecular mechanisms governing regeneration in this species. Full article