Immune Cell Adhesion Research Articles

Direct activation of Toll-like receptor 2 signaling stimulated by contact with the interfacial structures of chitin nanofibers

The innate immune system, which eliminates pathogens and abnormal cells, is involved in the pathogenesis of various diseases and infections, where Toll-like receptors (TLRs) play a critical regulatory role. In this study, we investigated the potential of chitin nanofiber (CtNF) to induce an immune response, which is expected to act as an agonist of TLR2. Crab-derived CtNF, surface-deacetylated CtNF, and surface-carboxylated cellulose NF were employed as TLR2-mediated immune stimulator, signal regulator, and cell adhesion promoter, respectively, to fabricate cell culture scaffolds for HEK293 cells with TLR2 and human monocyte THP-1 cells with or without TLR2. Surface deacetylation of CtNF drastically diminished the immunological response of HEK293 cells, suggesting that the N-acetyl groups on the solid CtNF surface were pivotal for TLR2-mediated stimulation. A comparison of wild-type and TLR2-KO THP-1 cells on cell culture substrates with N-acetyl groups ranging from 0 to 1.39 mmol g−1 revealed that immune signaling for nuclear factor-κB and interferon regulatory factor pathways was strongly dependent on the surface N-acetyl group content. The immunostimulatory level at the interface of solid CtNF and immune cells could be regulated by simply mixing CtNF and surface-deacetylated CtNF, which is a significant advantage for its potential use as a novel immunostimulant.

Regulation of cell-mediated immune responses in dairy bulls via long non-coding RNAs from submandibular lymph nodes, peripheral blood, and the spleen

Cell-mediated immune responses (CMIRs) are critical to building a robust immune system and reducing disease susceptibility in cattle. Long non-coding RNAs (lncRNAs) regulate various biological processes. However, to the best of our knowledge, the characterization and functions of lncRNAs and their regulations on the bovine CMIR have not been investigated comprehensively. In this study, experimental bulls were immunized with a heat-killed preparation of Candida albicans (HKCA) to induce delayed-type hypersensitivity (DTH). Three bulls were classified as high- CMIR responders and three were low-CMIR responders, based on their classical DTH skin reactions. LncRNAs were identified in the submandibular lymph nodes, peripheral blood, and spleen of high- and low-CMIR animals using strand-specific RNA sequencing. A total of 21,003 putative lncRNAs were identified across tissues, and 420, 468, and 599 lncRNAs were differentially expressed between the two groups in the submandibular lymph node, peripheral blood, and spleen tissues, respectively. Functional analysis of the differentially expressed lncRNA (DElncRNA) target genes showed that a number of immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched, including immune response, cell adhesion, nucleosome, DNA packaging, antigen processing and presentation, and complement and coagulation cascades. Tissue specificity analysis indicated that lncRNA transcripts have stronger tissue specificity than mRNA. Furthermore, an interaction network was constructed based on DElncRNAs and DEGs, and 11, 14, and 11 promising lncRNAs were identified as potential candidate genes influencing immune response regulation in submandibular lymph nodes, peripheral blood, and spleen tissues, respectively. These results provide a foundation for further research into the biological functions of lncRNAs associated with bovine CMIR and identify candidate lncRNA markers for cell-mediated immune responses.

Subverting Attachment to Prevent Attacking: Alteration of Effector Immune Cell Migration and Adhesion as a Key Mechanism of Tumor Immune Evasion.

Cell adhesion regulates specific migratory patterns, location, communication with other cells, physical interactions with the extracellular matrix, and the establishment of effector programs. Proper immune control of cancer strongly depends on all these events occurring in a highly accurate spatiotemporal sequence. In response to cancer-associated inflammatory signals, effector immune cells navigating the bloodstream shift from their patrolling exploratory migration mode to establish adhesive interactions with vascular endothelial cells. This interaction enables them to extravasate through the blood vessel walls and access the cancer site. Further adhesive interactions within the tumor microenvironment (TME) are crucial for coordinating their distribution in situ and for mounting an effective anti-tumor immune response. In this review, we examine how alterations of adhesion cues in the tumor context favor tumor escape by affecting effector immune cell infiltration and trafficking within the TME. We discuss the mechanisms by which tumors directly modulate immune cell adhesion and migration patterns to affect anti-tumor immunity and favor tumor evasion. We also explore indirect immune escape mechanisms that involve modifications of TME characteristics, such as vascularization, immunogenicity, and structural topography. Finally, we highlight the significance of these aspects in designing more effective drug treatments and cellular immunotherapies.

Proteomic Profiling of Lymph Nodes Differentiates Classic Hodgkin Lymphoma With and Without Skeletal Involvement.

Classic Hodgkin lymphoma (CHL) is a highly curable disease, even in advanced stages. Controversy remains over whether bone involvement negatively affects overall and progression-free survival in patients treated with intensive chemotherapy regimens. Whether cases that present with bone lesions harbor specific tumor microenvironmental features is unknown. We investigated protein expression in diagnostic lymph node biopsies from CHL patients with and without skeletal involvement at diagnosis to identify potential markers of skeletal disease. Protein expression patterns in diagnostic formalin-fixed paraffin-embedded lymphoma lymph node samples from CHL patients were analyzed by nano-liquid chromatography-tandem mass spectrometry. Patients were grouped according to skeletal involvement, which was defined as the presence of one or more FDG-avid lesions on a diagnostic FDG-PET/CT scan. Protein profiles identified patients with skeletal disease at diagnosis and showed disrupted cellular pathways, including immune system processes, cell adhesion, and cell growth/survival. Immunohistochemical evaluation also demonstrated differential expressions of angiotensin-converting enzyme (ACE), intercellular adhesion molecule 3 (ICAM3), integrin alpha-X (ITGAX), and calreticulin (CALR). In conclusion, proteomics identified altered protein expression profiles in lymph nodes among CHL cases presenting with disease disseminated to the skeletal system, which implies altered disease pathogenesis for these patients.

VCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition.

Studies in animal models have suggested a linkage between the inflammatory response to injury and subsequent nephron loss during the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Failure of normal repair during the CKD transition correlates with de novo expression of vascular cell adhesion protein-1 (VCAM-1) by a subset of injured proximal tubule cells. This study identified the role of VCAM-1 expression in promoting the failed repair state. Single-cell transcriptome analysis of patients with AKI and CKD and whole kidney RNA and protein analyses of mouse models of CKD confirmed a marked increase of VCAM-1 expression in the proximal tubules of injured kidneys. In immortalized mouse proximal tubular cells and primary cultured renal cells (PCRCs), VCAM-1 expression was induced by proinflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Analyses of bulk RNA sequencing of TNF-α-treated primary cultured renal cells or pseudo-bulk RNA sequencing of biopsies from Kidney Precision Medicine Project datasets indicated activation of NF-κB and an enrichment of inflammatory response and cell adhesion pathways in VCAM-1-positive cells. Pharmacological inhibition of NF-κB signaling or genetic deletion of myeloid differentiation factor 88 and TIR domain-containing adapter-inducing interferon-β suppressed TNF-α- and IL-1β-induced VCAM-1 expression in vitro. TNF-α stimulation or overexpression of VCAM-1 significantly increased splenocyte adhesion to the mouse proximal tubular monolayer in culture. These results demonstrate that persistence of proinflammatory cytokines after AKI can induce NF-κB-dependent VCAM-1 expression by proximal tubule cells, mediating increased immune cell adhesion to the tubule and thus promoting further tubule injury and greater risk of progression from AKI to CKD.NEW & NOTEWORTHY We demonstrated the induction of VCAM-1 and its biological function in proximal tubules. We found that proinflammatory cytokines (TNF-α and IL-1β) significantly induced VCAM-1 expression via NF-κB signaling pathway. TNF-α treatment or overexpression of VCAM-1 in immortalized MPT cells increased CD45+ splenocyte adhesion. Pharmacological inhibition of NF-κB or genetic deletion of Vcam1 suppressed TNF-α-induced splenocyte adhesion in vitro, suggesting that VCAM-1 mediates proximal tubular-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition.

IFIT2 mediates iron retention and cholesterol efflux in atherosclerosis

BackgroundAbnormalities in iron and lipid metabolism are recognized as key contributors to atherosclerosis (AS). Therefore, this study proposes to characterize the biomarker related to iron and lipid metabolism in AS using bioinformatics, animal, and cell experiments. MethodsThe limma package was utilized to identify differentially expressed genes (DEGs) in GSE70126 and GSE70619 datasets, and biomarkers were screened using enrichment analysis and PPI networks. IFIT2 was knocked down using shRNA lentivirus in a high fat diet (HFD)-induced APOE-/- AS model to investigate its effects of IFIT2 on the pathology, iron retention, and lipid accumulation. Iron storage-related and cholesterol efflux-related proteins were evaluated following exogenous modulation of IFIT2 expression in ox-LDL-induced foamy macrophages. ResultsCompared to non-foamy macrophages from the aorta, 189 and 4152 DEGs were identified in foamy macrophages within the GSE70126 and GSE70619 datasets, respectively. Moreover, intersecting DEGs may modulate immune responses, cell adhesion, vascular permeability, and oxidative stress through NF-kappa B, Wnt, TNF and HIF-1 signaling pathways. Notably, IFIT2 was significantly upregulated in foamy macrophages and AS models. In vivo, IFIT2 co-localized with foamy macrophages, and its knockdown led to reductions in plasma lipid levels, plaque area, immune infiltration, iron retention, and lipid accumulation. In vitro, IFIT2 knockdown alleviated the ox-LDL-induced increase in iron storage-related proteins (Ferritin-L and Ferritin-H) and iron (Fe2+ and Fe3+) in foamy macrophages. Furthermore, IFIT2 knockdown reduced lipid accumulation and upregulated cholesterol efflux-related proteins (PPARγ, LXRα, ABCA1, and ABCG1) in foamy macrophages. ConclusionIFIT2 knockdown attenuates iron retention and lipid accumulation in AS plaques, and facilitated cholesterol efflux from foamy macrophages via the PPARγ/LXRα/ABCA1-ABCG1 pathway.

Lung Fibrosis Is Linked to Increased Endothelial Cell Activation and Dysfunctional Vascular Barrier Integrity.

Pulmonary fibrosis (PF) can be a fatal disease characterized by progressive lung scarring. It is still poorly understood how the pulmonary endothelium is involved in the disease pathogenesis. Differences of the pulmonary vasculature between patients and donors were analyzed using transmission electron microscopy, immunohistochemistry, and single-cell RNA sequencing. Vascular barrier resistance, endothelial-immune cell adhesion, and sensitivity to an inflammatory milieu were studied invitro. Integrity and activation markers were measured by ELISA in human plasma. Transmission electron microscopy demonstrated abnormally swollen endothelial cells (ECs) in fibrotic lungs compared with donors. A more intense CD31 and von Willebrand Factor (vWF) and patchy vascular endothelial (VE)-Cadherin staining in fibrotic lungs supported the presence of a dysregulated endothelium. Integrity markers CD31, VE-Cadherin, Thrombomodulin, and VEGFR-2 (vascular endothelial growth factor receptor-2) and activation marker vWF gene expression was increased in different endothelial subpopulations (e.g., arterial, venous, general capillary, aerocytes) in PF. This was associated with a heightened sensitivity of fibrotic ECs to TNF-α or IFN-γ and elevated immune cell adhesion. The barrier strength was overall reduced in ECs from fibrotic lungs. vWF and IL-8 were increased in the plasma of patients, whereas VE-Cadherin, Thrombomodulin, and VEGFR-2 were decreased. VE-Cadherin staining was also patchy in biopsy tissue and was decreased in plasma samples of patients with PF 6 months after the initial diagnosis. Our data demonstrate highly abnormal ECs in PF. The vascular compartment is characterized by hyperactivation and increased immune cell adhesion, as well as dysfunctional endothelial barrier function. Reestablishing EC homeostasis and function might represent a new therapeutic option for fibrotic lung diseases.

Vascular-adhesion protein 1 in giant cell arteritis and polymyalgia rheumatica.

Vascular adhesion protein-1 (VAP-1) is a type 2 transmembrane sialoglycoprotein with oxidative deamination functionality, encoded by the amine oxidase copper-containing 3 (AOC3) gene. VAP-1 is widely expressed across various tissues, particularly in highly vascularized tissues and organs essential for lymphocyte circulation. In the vascular system, VAP-1 is predominantly found in vascular smooth muscle cells and endothelial cells, with higher expression levels in vascular smooth muscle cells. Under inflammatory conditions, VAP-1 rapidly translocates to the endothelial cell surface, facilitating leukocyte adhesion and migration through interactions with specific ligands, such as sialic acid-binding immunoglobulin-type lectins (Siglec)-9 on neutrophils and monocytes, and Siglec-10 on B cells, monocytes, and eosinophils. This interaction is crucial for leukocyte transmigration into inflamed tissues. Furthermore, VAP-1's enzymatic activity generates hydrogen peroxide and advanced glycation end-products, contributing to cytotoxic damage and vascular inflammation. In this context, the soluble form of VAP-1 (sVAP-1), produced by matrix metalloproteinase cleavage from its membrane-bound counterpart, also significantly influences leukocyte migration. This review aims to elucidate the multifaceted pathophysiological roles of VAP-1 in vascular inflammation, particularly in giant cell arteritis (GCA) and associated polymyalgia rheumatica (PMR). By exploring its involvement in immune cell adhesion, migration, and its enzymatic contributions to oxidative stress and tissue damage, we investigate the importance of VAP-1 in GCA. Additionally, we discuss recent advancements in imaging techniques targeting VAP-1, such as [68Ga]Ga-DOTA-Siglec-9 PET/CT, which have provided new insights into VAP-1's role in GCA and PMR. Overall, understanding VAP-1's comprehensive roles could pave the way for improved strategies in managing these conditions.

A Whole-Transcriptomic Analysis of Canine Oral Melanoma: A Chance to Disclose the Radiotherapy Effect and Outcome-Associated Gene Signature.

Oral melanoma (OM) is the most common malignant oral tumour among dogs and shares similarities with human mucosal melanoma (HMM), validating the role of canine species as an immunocompetent model for cancer research. In both humans and dogs, the prognosis is poor and radiotherapy (RT) represents a cornerstone in the management of this tumour, either as an adjuvant or a palliative treatment. In this study, by means of RNA-seq, the effect of RT weekly fractionated in 9 Gray (Gy), up to a total dose of 36 Gy (4 weeks), was evaluated in eight dogs affected by OM. Furthermore, possible transcriptomic differences in blood and biopsies that might be associated with a longer overall survival (OS) were investigated. The immune response, glycosylation, cell adhesion, and cell cycle were the most affected pathways by RT, while tumour microenvironment (TME) composition and canonical and non-canonical WNT pathways appeared to be modulated in association with OS. Taking these results as a whole, this study improved our understanding of the local and systemic effect of RT, reinforcing the pivotal role of anti-tumour immunity in the control of canine oral melanoma (COM).

Integrative analysis of single-Cell RNA sequencing and experimental validation in the study of abdominal aortic aneurysm progression

BackgroundAbdominal aortic aneurysm (AAA) is a complex vascular disorder characterized by the progressive dilation of the abdominal aorta, with a high risk of rupture and mortality.Understanding the cellular interactions and molecular mechanisms underlying AAA development is critical for identifying potential therapeutic targets. MethodsThis study utilized datasets GSE197748, GSE164678 and GSE183464 from the GEO database, encompassing bulk and single-cell RNA sequencing data from AAA and control samples. We performed principal component analysis, differential expression analysis, and functional enrichment analysis to identify key pathways involved in AAA. Cell-cell interactions were investigated using CellPhoneDB, focusing on fibroblasts, vascular smooth muscle cells (VSMCs), and macrophages. We further validated our findings using a mouse model of AAA induced by porcine pancreatic enzyme infusion, followed by gene expression analysis and co-immunoprecipitation experiments. ResultsOur analysis revealed significant alterations in gene expression profiles between AAA and control samples, with a pronounced immune response and cell adhesion pathways being implicated. Single-cell RNA sequencing data highlighted an increased proportion of pro-inflammatory macrophages, along with changes in the composition of fibroblasts and VSMCs in AAA. CellPhoneDB analysis identified critical ligand-receptor interactions, notably collagen type I alpha 1 chain (COL1A1)/COL1A2-CD18 and thrombospondin 1 (THBS1)-CD3, suggesting complex communication networks between fibroblasts and VSMCs. In vivo experiments confirmed the upregulation of these genes in AAA mice and demonstrated the functional interaction between COL1A1/COL1A2 and CD18. ConclusionThe interaction between fibroblasts and VSMCs, mediated by specific ligand-receptor pairs such as COL1A1/COL1A2-CD18 and THBS1-CD3, plays a pivotal role in AAA pathogenesis.

Epithelial CEBPD activates fibronectin and enhances macrophage adhesion in renal ischemia-reperfusion injury

Ischemia-reperfusion injury (IRI) is a cause of acute kidney injury in patients after renal transplantation and leads to high morbidity and mortality. Damaged kidney resident cells release cytokines and chemokines, which rapidly recruit leukocytes. Fibronectin (FN-1) contributes to immune cell migration, adhesion and growth in inflamed tissues. CCAAT/enhancer-binding protein delta is responsive to inflammatory cytokines and stresses and plays functional roles in cell motility, extracellular matrix production and immune responses. We found that the expression of CCAAT/enhancer-binding protein delta was increased in renal epithelial cells in IRI mice compared with sham mice. Following IRI, the colocalization of FN-1 with the macrophage marker F4/80 was increased in renal injury model wild-type mice but was significantly attenuated in Cebpd-deficient mice. Inactivation of CEBPD can repress hypoxia-induced FN-1 expression in HK-2 cells. Moreover, the inactivation of CEBPD and FN-1 also reduces macrophage accumulation in HK-2 cells. These findings suggest that the involvement of CEBPD in macrophage accumulation through the activation of FN-1 expression and the inhibition of CEBPD can protect against renal IRI.

Interleukin receptor therapeutics attenuate inflammation in canine synovium following cruciate ligament injury

ObjectiveIn the knee, synovial fibrosis after ligamentous injury is linked to progressive joint pain and stiffness. The objective of this study was to evaluate changes in synovial architecture, mechanical properties, and transcriptional profiles following naturally occurring cruciate ligament injury in canines and to test potential therapeutics that target drivers of synovial inflammation and fibrosis. DesignSynovia from canines with spontaneous cruciate ligament tears and from healthy knees were assessed via histology (n=10/group) and micromechanical testing (n=5/group) to identify changes in tissue architecture and stiffness. Additional samples (n=5/group) were subjected to RNA-sequencing to define the transcriptional response to injury. Finally, synovial tissue samples from injured animals (n=6 (IL1) or n=8 (IL6)/group) were assessed in vitro for response to therapeutic molecules directed against interleukin (IL) signaling (IL1 or IL6). ResultsCruciate injury resulted in increased synovial fibrosis, vascularity, inflammatory cell infiltration, and intimal hyperplasia. Additionally, the stiffness of both the intima and subintima regions were higher in diseased compared to healthy tissue. Differential gene expression analysis showed that diseased synovium had an upregulation of immune response and cell adhesion pathways and a downregulation of Rho protein transduction pathways. In vitro application of small molecule therapeutics targeting IL1 (anakinra) or IL6 (tocilizumab) dampened expression of inflammatory and matrix deposition mediators. ConclusionSpontaneous cruciate ligament injury in canines is associated with synovial inflammation and fibrosis in a relevant model for testing emerging intra-articular treatments. Small molecule therapeutics targeting IL pathways may be ideal interventions for delivery to the joint space after injury.

Impact of Matrix Gel Variations on Primary Culture of Microvascular Endothelial Cell Function.

The endothelium regulates crucial aspects of vascular function, including hemostasis, vasomotor tone, proliferation, immune cell adhesion, and microvascular permeability. Endothelial cells (ECs), especially in arterioles, are pivotal for flow distribution and peripheral resistance regulation. Investigating vascular endothelium physiology, particularly in microvascular ECs, demands precise isolation and culturing techniques. Freshly isolated ECs are vital for examining protein expression, ion channel behavior, and calcium dynamics. Establishing primary endothelial cell cultures is crucial for unraveling vascular functions and understanding intact microvessel endothelium roles. Despite the significance, detailed protocols and comparisons with intact vessels are scarce in microvascular research. We developed a reproducible method to isolate microvascular ECs, assessing substrate influence by cultivating cells on fibronectin and gelatin matrix gels. This comparative approach enhances our understanding of microvascular endothelial cell biology. Microvascular mesenteric ECs expressed key markers (VE-cadherin and eNOS) in both matrix gels, confirming cell culture purity. Under uncoated conditions, ECs were undetected, whereas proteins linked to smooth muscle cells and fibroblasts were evident. Examining endothelial cell (EC) physiological dynamics on distinct matrix substrates revealed comparable cell length, shape, and Ca2+ elevations in both male and female ECs on gelatin and fibronectin matrix gels. Gelatin-cultured ECs exhibited analogous membrane potential responses to acetylcholine (ACh) or adenosine triphosphate (ATP), contrasting with their fibronectin-cultured counterparts. In the absence of stimulation, fibronectin-cultured ECs displayed a more depolarized resting membrane potential than gelatin-cultured ECs. Gelatin-cultured ECs demonstrated electrical behaviors akin to intact endothelium from mouse mesenteric arteries, thus advancing our understanding of endothelial cell behavior within diverse microenvironments.

Role of ICAM1 on Immune Cells in Glioblastoma: A Review Study

Introduction: Glioblastoma, also known as glioblastoma multiforme (GBM), is a highly aggressive and incurable form of brain tumor that grows rapidly. Intracellular cell adhesion molecule 1 (ICAM1) is a glycoprotein and adhesion receptor that plays a multifaceted role in immune response and can serve as a therapeutic target. Due to the severity and poor prognosis associated with GBM, the interaction between ICAM1 and GBM has been a topic of interest in the hope of providing therapeutic value. Methods: This review synthesizes existing literature and studies through searches in the PubMed, Google Scholar, Web of Science, Ovid-Medline, and EBSCO databases to explore the role of ICAM1 on immune cells in the context of GBM. Search terms such as “GBM,” “ICAM1,” “tumor microenvironment,” as well as “adhesion molecules” and “GBM treatment” were employed. Literature was selected based on its applicability to key aspects of the research topic. Results: This comprehensive review anticipated uncovering the complex role of ICAM1 in immune cell adhesion in GBM. By promoting the adhesion of immune cells, such as T lymphocytes and natural killer cells, ICAM1 can potentially enhance the body's natural defense mechanisms against GBM. However, the tumor microenvironment (and interaction with other molecules) can also manipulate and alter ICAM1 in ways that inhibits an effective immune response, potentially resulting in tumor progression. Discussion: Understanding the role of ICAM1 in GBM can present new strategies for immune-based therapies in GBM, potentially leading to improved treatment outcomes. Moreover, gaining insight into how adhesion molecules, such as ICAM1, respond to the tumor microenvironment can advance GBM therapy and also provide insights into treatment options for various cancers. Conclusion: ICAM1 exerts both pro-tumorigenic and anti-tumorigenic effects, shaping tumor progression and immune evasion. Understanding these dual roles can guide the development of targeted therapies for GBM.

The Impact of Acute EBV Infection on Changes in the Serum Proteome in Children-A Pilot Study.

This study investigates the impact of Epstein-Barr virus (EBV) infection on children's proteomes across different phases of the disease, utilising seventy-nine blood samples categorised into three groups: EBV-naive patients, acute infectious mononucleosis (IM) cases, and convalescents followed up for 12 months post-IM. The aim is to identify proteins influenced by EBV infection, shedding light on the chronic processes triggered by the virus. The results reveal thirty-nine proteins distinguishing between naive patients and those with IM, including actin, lumican, peroxiredoxin-2, fibulin-1, gelsolin, and alpha-2-macroglobulin, which are involved in immune responses, cell adhesion, and inflammation. Elevated oxidative stress markers like peroxiredoxin-2 in IM patients suggest potential links to EBV's induction of reactive oxygen species. Increased levels of apolipoproteins A-I, A-IV, C-IV, and M during IM imply associations with viral infection, while complement system proteins (C1q, C1r, and C8 gamma chain) are also elevated, reflecting their role in the immune response and viral clearance. This study's focus on children provides unique insights into EBV's impact on young populations, emphasising proteomics' role in uncovering protein associations and understanding the virus's long-term consequences. However, specific relationships between identified proteins and EBV infection require further investigation.

Identification of Immune-Related Gene Signature in Schizophrenia.

Schizophrenia (SCZ) is a type of psychiatric disorder characterized by multiple symptoms. Our aim is to decipher the relevant mechanisms of immune-related gene signatures in SCZ. The SCZ dataset and its associated immunoregulatory genes were retrieved using Gene Expression Omnibus (GEO) and single-sample gene set enrichment analysis (ssGSEA). Co-expressed gene modules were determined through weighted gene correlation network analysis (WGCNA). To elucidate the functional characteristics of these clusters, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used. Additionally, gene set enrichment analysis (GSEA) and Gene Set Variation Analysis (GSVA) were conducted to identify enriched pathways for the immune subgroups. A protein-protein interaction (PPI) network analysis was performed to identify core genes relevant to SCZ. A significantly higher immune score was observed in SCZ compared to control samples. Seven distinct gene modules were identified, with genes highlighted in green selected for further analysis. Using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) method, degrees of immune cell adhesion and accumulation related to 22 different immune cell types were calculated. Significantly enriched bioprocesses concerning the immunoregulatory genes with differential expressions included interferon-beta, IgG binding, and response to interferon-gamma, according to GO and KEGG analyses. Eleven hub genes related to immune infiltration emerged as key players among the three top-ranked GO terms. This study underscores the involvement of immunoregulatory reactions in SCZ development. Eleven immune-related genes (IFITM1 (interferon induced transmembrane protein 1), GBP1 (guanylate binding protein 1), BST2 (bone marrow stromal cell antigen 2), IFITM3 (interferon induced transmembrane protein 3), GBP2 (guanylate binding protein 2), CD44 (CD44 molecule), FCER1G (Fc epsilon receptor Ig), HLA-DRA (major histocompatibility complex, class II, DR alpha), FCGR2A (Fc gamma receptor IIa), IFI16 (interferon gamma inducible protein 16), and FCGR3B (Fc gamma receptor IIIb)) were identified as hub genes, representing potential biomarkers and therapeutic targets associated with the immune response in SCZ patients.

Characterisation of the tracheal transcriptional response of chickens to chronic infection with Mycoplasma synoviae

Mycoplasma synoviae causes infectious synovitis and respiratory tract infections in chickens and is responsible for significant economic losses in the poultry industry. Effective attachment and colonisation of the trachea is critical for the persistence of the organism and progression of the disease it causes. The respiratory tract infection is usually sub-clinical, but concurrent infection with infectious bronchitis virus (IBV) is known to enhance the pathogenicity of M. synoviae. This study aimed to explore differentially expressed genes in the tracheal mucosa, and their functional categories, during chronic infection with M. synoviae, using a M. synoviae-IBV infection model. The transcriptional profiles of the trachea were assessed 2 weeks after infection using RNA sequencing. In chickens infected with M. synoviae or IBV, only 1 or 8 genes were differentially expressed compared to uninfected chickens, respectively. In contrast, the M. synoviae-IBV infected chickens had 621 upregulated and 206 downregulated genes compared to uninfected chickens. Upregulated genes and their functional categories were suggestive of uncontrolled lymphoid cell proliferation and an ongoing pro-inflammatory response. Genes associated with anti-inflammatory effects, pathogen removal, apoptosis, regulation of the immune response, airway homoeostasis, cell adhesion and tissue regeneration were downregulated. Overall, transcriptional changes in the trachea, 2 weeks after infection with M. synoviae and IBV, indicate immune dysregulation, robust inflammation and a lack of cytotoxic damage during chronic infection. This model provides insights into the pathogenesis of chronic infection with M. synoviae.

Immune Cell Migration to Cancer.

Immune cell migration is required for the development of an effective and robust immune response. This elegant process is regulated by both cellular and environmental factors, with variables such as immune cell state, anatomical location, and disease state that govern differences in migration patterns. In all cases, a major factor is the expression of cell surface receptors and their cognate ligands. Rapid adaptation to environmental conditions partly depends on intrinsic cellular immune factors that affect a cell's ability to adjust to new environment. In this review, we discuss both myeloid and lymphoid cells and outline key determinants that govern immune cell migration, including molecules required for immune cell adhesion, modes of migration, chemotaxis, and specific chemokine signaling. Furthermore, we summarize tumor-specific elements that contribute to immune cell trafficking to cancer, while also exploring microenvironment factors that can alter these cellular dynamics within the tumor in both a pro and antitumor fashion. Specifically, we highlight the importance of the secretome in these later aspects. This review considers a myriad of factors that impact immune cell trajectory in cancer. We aim to highlight the immunotherapeutic targets that can be harnessed to achieve controlled immune trafficking to and within tumors.

Proteomic Analysis of Idiopathic Nephrotic Syndrome Triggered by Primary Podocytopathies in Adults: Regulatory Mechanisms and Diagnostic Implications.

Idiopathic nephrotic syndrome (NS) is a heterogeneous group of glomerular disorders which includes two major phenotypes: minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). MCD and FSGS are classic types of primary podocytopathies. We aimed to explore the molecular mechanisms in NS triggered by primary podocytopathies and evaluate diagnostic value of the selected proteomic signatures by analyzing blood proteome profiling. Totally, we recruited 90 participants in two cohorts. The first cohort was analyzed using label-free quantitative (LFQ) proteomics to discover differential expressed proteins and identify enriched biological process in NS which were further studied in relation to clinical markers of kidney injury. The second cohort was analyzed using parallel reaction monitoring-based quantitative proteomics to verify the data of LFQ proteomics and assess the diagnostic performance of the selected proteins using receiver-operating characteristic curve analysis. Several biological processes (such as immune response, cell adhesion, and response to hypoxia) were found to be associated with kidney injury during MCD and FSGS. Moreover, three proteins (CSF1, APOC3, and LDLR) had over 90% sensitivity and specificity in detecting adult NS triggered by primary podocytopathies. The identified biological processes may play a crucial role in MCD and FSGS pathogenesis. The three blood protein markers are promising for diagnosing adult NS triggered by primary podocytopathies.

Activating the intratumoral IFN[gamma]R-pathway in adrenocortical carcinoma potently enhances antitumor functionality of CAR-T cells by modulating immune cell adhesion and responsiveness

Activating the intratumoral IFN[gamma]R-pathway in adrenocortical carcinoma potently enhances antitumor functionality of CAR-T cells by modulating immune cell adhesion and responsiveness