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PubMed2002

Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma.

In the present study, epithelium derived lesions of various pathological manifestations were examined histologically and immunohistochemically for mononuclear cell infiltration. The infiltrate under the transformed epithelium of oral lesions, was examined for differences in the composition of immune mononuclear cells as the epithelium moves from hyperkeratosis through various degrees of dysplasia to squamous cell carcinoma. The study was performed on 53 human tongue tissues diagnosed as hyperkeratosis (11 cases), mild dysplasia (nine cases), moderate and severe dysplasia (14 cases) and squamous cell carcinoma (19 cases). A similar analysis was performed on 30 parotid gland tissues diagnosed as pleomorphic adenoma (14 cases) and carcinoma ex-pleomorphic adenoma (16 cases). Immunohistochemical analysis of various surface markers of the tumour infiltrating immune cells was performed and correlated with the transformation level as defined by morphology and the expression of p53 in the epithelium. The results revealed that, in the tongue lesions, the changes in the epithelium from normal appearance to transformed were accompanied by a corresponding increase in the infiltration of CD4, CD8, CD14, CD19+20, and HLA/DR positive cells. The most significant change was an increase in B lymphocytes in tongue lesions, that was in accordance with the transformation level (P<0.001). In the salivary gland, a significant number of cases did not show an infiltrate. In cases where an infiltrate was present, a similar pattern was observed and the more malignant tissues exhibited a higher degree of immune cell infiltration.

Carcinoma↗

PubMed2005

Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension.

BACKGROUND: Prenatal environment has been shown to modify adult blood pressure profile, but the underlying mechanisms are not well understood. The role of renal immune cell infiltration, oxidative stress, and nitric oxide bioavailability in the pathogenesis was investigated. METHODS: Adult hypertension in rat offspring was induced by maternal low protein diet. Oxidative stress was determined by quantitative immunoblotting for nitrotyrosine, and T-cell and macrophage content by immunostaining, in offspring kidneys before and after the onset of hypertension. Nitric oxide metabolites (NOx) were measured in 24-hour urines. A group of offspring was treated with the immunosuppressive drug mycophenolate mofetil (MMF) to reduce inflammation, or with the superoxide dismutase mimetic Tempol to reduce oxidative stress, for a 3-week period before the onset of hypertension. RESULTS: During the prehypertensive stage, at 4 weeks of age, the low protein diet pups exhibited an increase in kidney nitrotyrosine content and in number of immune cells, both of which persisted in untreated animals after hypertension was established, at 8 weeks of age. Urine NOx was increased at 4 weeks and unchanged at 8 weeks of age. Both MMF and Tempol treatment prevented the immune cell infiltration, the increase in kidney nitrotyrosine abundance, and the development of hypertension. The effect on blood pressure persisted throughout the 4- to 10-week observation period after discontinuation of the treatments. CONCLUSION: Renal oxidative stress and infiltrating immune cells may play a pathogenetic role in prenatally programmed hypertension. Nitric oxide bioavailability does not appear impaired.

Animals↗

PubMed2003

The involvement of advanced glycation endproducts (AGEs) in renal injury of diabetic glomerulosclerosis: association with phenotypic change in renal cells and infiltration of immune cells.

BACKGROUND: Glycation of proteins is regarded as one of the major causes of the progression of diabetic nephropathy (DN) and of the phenotypic changes in glomerular mesangial cells (MC) and the cellular infiltration that occurs in MC from DN. It thus is very important to study the interrelationships and interaction between these causes. METHODS: The localization of advanced glycation endproducts (AGEs), cytoskeletal proteins, and immune cell infiltration was evaluated by immunohistochemical study in patients with DN. RESULTS: N(Epsilon)-(carboxymethyl)lysine (CML), Alpha-smooth muscle actin (SMA), and low-molecular-weight caldesmon (L-CLD) were localized in the mesangial area in DN. The intensity of mesangial SMA and L-CLD expression was significantly correlated with the index of diabetic glomerulosclerosis (IDGS), while the expression of pentosidine was correlated with the IDGS and with 24-h urinary protein. Pentosidine was localized in glomerular basement membrane (GBM) only in DN and had a significant correlation with the mesangial expression of SMA and L-CLD. Pyrraline deposition on the tubular basement membrane, and the expression of SMA and L-CLD, and the infiltration of immune cells were observed in interstitial areas in DN. The intensity of L-CLD expression had a close relationship with pyrraline deposition and immune cell infiltration. The expression of SMA and L-CLD in interstitial areas was significantly correlated with the percent interstitial volume. CONCLUSIONS: AGEs are involved in renal injury in DN, and their effect is, at least in part, exercised via phenotypic changes in intrinsic renal cells and by the infiltration of immune cells.

Actins↗

PubMed2000

Immune cell infiltrates and prognosis in primary carcinoma of the lung.

The prognostic significance of immune cell infiltrates in surgically resected human lung cancer was investigated in 710 patients. Lymphoid infiltrates were quantified on both standard H&E stained sections and, in a subset of 95 cases, using immunohistochemistry and antibodies to CD3, CD8, CD57, CD68, CD79a and S100 to identify various immune cell types. Subjective grading (low, moderate, high) of lymphoid cell infiltrates on H&E sections of tumour and measurement, using image analysis, of overall level of tumour infiltration by any of the immunohistochemically labelled specific immune cell types of the stained sections showed no prognostic significance. However, when a distinction between peritumoural and intratumoural infiltration by particular cell types was made, intratumoural infiltration by high levels of CD3+ and S100+ cells was associated with longer post-operative survival (P = 0.02 and P = 0.045, respectively). In lung cancer, subjective assessment of tumour lymphoid infiltration and overall levels of infiltration by particular immune cell types carries no prognostic significance. Intratumoural infiltration by relatively high numbers of CD3+ T-lymphocytes and Langerhans cells (S100+) is associated with a better patient outcome.

Adult↗

PubMed2025

Integrating necroptosis and immune landscapes: a multi-omics-derived NecropImmScore stratifies prognosis and therapy in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) remains the deadliest gynecologic malignancy, largely due to its immunosuppressive tumor microenvironment (TME) and resistance to therapy. Necroptosis, a regulated lytic cell death pathway mediated by the RIPK1-RIPK3-MLKL axis, can trigger immunogenic cell death, but its specific role in shaping the OC immune landscape and its clinical translation potential are posorly understood. METHODS: We employed multi-omics analysis (transcriptomics, genomics, clinical data) from TCGA-OV (n = 380), ICGC OV-AU, and IMvigor210 cohorts, combined with rigorous in vitro functional validation using OC cell lines (SKOV3, HEY), macrophages (THP-1 derived), and T cells (Jurkat). Computational immunology approaches (ESTIMATE, CIBERSORT, ssGSEA) quantified immune infiltration. We identified MLKL-associated immune genes, performed survival analysis (Kaplan-Meier, Cox regression), and constructed a necroptosis-immune signature (NecropImmScore) using consensus clustering and PCA of 102 prognostic genes. Drug sensitivity was predicted via pRRophetic and CellMiner. RESULTS: MLKL emerged as a protective prognostic biomarker (p = 0.018), significantly correlated with enhanced immune infiltration (ImmuneScore, StromalScore, ESTIMATEScore; p < 2.22e-16), M1 macrophage polarization (p = 0.006), activated CD4 + T cells (p = 0.003), and elevated immune checkpoint expression (PD-L1, CTLA4, LAG3, TIGIT). In vitro, MLKL overexpression in OC cells promoted M1 polarization (p < 0.05), activated Jurkat T cells (upregulated CCR4/5/7/9, CD69, CD3D/E, GZMB; p < 0.05), and induced key chemokines (CXCL9/10/11/13) critical for immune cell recruitment. Integration of MLKL-related and immune-related DEGs (n = 632) revealed enrichment in T-cell activation, chemokine signaling, and antigen presentation pathways (FDR < 0.05). Consensus clustering based on 102 survival-associated genes defined three molecular subtypes (Clusters A-C) with divergent survival (p = 0.019), necroptosis activity, and immune infiltration (Cluster C: best prognosis, highest MLKL/ImmuneScore). The derived NecropImmScore robustly stratified patients: high-score correlated with superior overall survival (TCGA: p < 0.001; ICGC: p = 0.014), inflamed TME phenotype, elevated checkpoint expression, and improved response to anti-PD-L1 in IMvigor210. Critically, high NecropImmScore predicted higher BRCA1 mutation frequency (AUC = 0.802), synergy with BRCA1 status for prognosis, higher homologous recombination deficiency (HRD) score, sensitivity to cisplatin (p = 0.014), paclitaxel (p = 0.016), gemcitabine (p = 0.017), and provided superior prognostic stratification when combined with TMB and HRD score (p < 0.001). CONCLUSION: This study establishes MLKL as a master regulator of anti-tumor immunity in OC, driving chemokine-mediated immune cell recruitment and TME reprogramming. The novel NecropImmScore is a multifaceted biomarker that effectively predicts prognosis, immunotherapy response, BRCA1 deficiency, and chemosensitivity, offering significant potential for guiding precision therapeutic strategies in OC.

Humans↗

PubMed2026

The role of KIAA1467 in breast cancer: insights from pan-cancer and single-cell sequencing analysis.

BACKGROUND: Improving the response rate of single-agent immune checkpoint blockade (ICB) urgently requires the discovery of new therapeutic targets for combinatorial regimens. Analyses of tumor microenvironment (TME)-associated biomarkers have verified that KIAA1467 drives the formation of an immune-excluded, non-inflamed TME in breast cancer (BRCA). This study systematically explores the expression pattern, prognostic value, immune regulatory function, biological effects, and drug resistance relevance of FAM234B (also known as KIAA1467) in BRCA. METHODS: We performed pan-cancer survival analysis using The Cancer Genome Atlas (TCGA) datasets. Multi-omics bioinformatics analyses were conducted to evaluate KIAA1467 expression across malignancies. Single-cell RNA sequencing (scRNA-seq) data from GSE176078 was utilized to localize KIAA1467 expression at the cellular level. Immunohistochemistry and western blot assays validated KIAA1467 expression in BRCA clinical specimens. Correlation analyses were implemented to assess relationships between KIAA1467 expression, clinicopathological features, immune modulators, tumor-infiltrating immune cells, and p53 mutation status. Functional enrichment analysis uncovered relevant signaling pathways. Bioinformatic half maximal inhibitory concentration (IC50) prediction and in vitro cellular experiments were applied to evaluate associations between KIAA1467 and chemotherapeutic drug sensitivity. RESULTS: TCGA pan-cancer survival analysis demonstrated that elevated KIAA1467 expression significantly predicted shortened overall survival in BRCA and multiple other tumor types. KIAA1467 displayed distinct expression patterns across cancers, with prominent upregulation in BRCA. scRNA-seq confirmed enriched KIAA1467 expression within BRCA cells, and its upregulation in BRCA tissues was further verified by immunohistochemistry and western blot. High KIAA1467 expression was positively correlated with advanced tumor grade and lymphatic metastasis. KIAA1467 showed negative correlations with most immune modulators and core immune checkpoint molecules, as well as tumor-infiltrating immune cells in the TME, implying its potential function in tumor immune evasion. Low KIAA1467 expression was tightly linked to p53 mutations. Enrichment analysis indicated participation of KIAA1467 in epithelial-mesenchymal transition, apoptosis and cell cycle arrest. Furthermore, high KIAA1467 expression corresponded to higher estimated IC50 values of cisplatin, gefitinib, paclitaxel and gemcitabine, consistent with reduced chemosensitivity observed in vitro. CONCLUSIONS: This study reveals the multifaceted oncogenic role of KIAA1467 in BRCA. KIAA1467 participates in remodeling an immunosuppressive TME, correlates with malignant progression and chemoresistance, and may serve as a promising candidate target to optimize ICB-based combination therapy for BRCA. These findings offer new perspectives for the clinical treatment and comprehensive management of BRCA.

KIAA1467↗

PubMed2002

Reduction of renal immune cell infiltration results in blood pressure control in genetically hypertensive rats.

Immunocompetent cells infiltrate the kidney in several models of experimental hypertension. We have previously shown that reduction of this infiltrate results in prevention of salt-sensitive hypertension induced by short-term angiotensin II infusion and nitric oxide inhibition (Quiroz Y, Pons H, Gordon KI, Rincón J, Chávez M, Parra G, Herrera-Acosta J, Gómez-Garre D, Largo R, Egido J, Johnson RJ, and Rodríguez-Iturbe B. Am J Physiol Renal Physiol 281: F38-F47, 2001; Rodríguez-Iturbe B, Pons H, Quiroz Y, Gordon K, Rincón J, Chávez M, Parra G, Herrera-Acosta J, Gómez-Garre D, Largo R, Egido J, and Johnson RJ. Kidney Int 59: 2222-2232, 2001). We therefore studied whether hypertension could be controlled in genetically hypertensive rats [spontaneously hypertensive rats (SHR)] by the administration of 20 mg x kg(-1) x day(-1) of the immunosuppressive drug mycophenolate mofetil (MMF group; n = 35). Other SHR received vehicle (n = 35), and Wistar-Kyoto rats (n = 20) were used as controls. MMF or vehicle was given in two separate 4-wk periods, separated by a 3-wk interval. Systemic hypertension was reduced to normal levels in both periods of MMF treatment in association with a reduction in lymphocyte, macrophage, and angiotensin II-positive cells infiltrating the kidney. Oxidative stress was also reduced by MMF, as indicated by a reduction in urinary malondialdehyde (MDA), renal MDA content, and superoxide-positive cells, and was highly correlated with blood pressure levels. We conclude that the renal immune infiltrate plays a major role in the hypertension in SHR.

Angiotensin II↗

PubMed2006

Secretory leukocyte protease inhibitor expression in various types of gastritis: a specific role of Helicobacter pylori infection.

OBJECTIVES: Secretory leukocyte protease inhibitor (SLPI) represents a multifunctional protein of the gastrointestinal mucosa exerting antimicrobial and anti-inflammatory effects. SLPI expression is generally induced during inflammation; however, Helicobacter pylori-mediated gastritis is associated with significantly decreased antral SLPI levels. The aim of the study was to investigate whether SLPI downregulation of gastric mucosa represents a specific phenomenon of H. pylori infection or is generally linked to gastric inflammation. METHODS: SLPI expression was retrospectively analysed by immunohistochemistry in 85 paraffin-embedded samples: H. pylori-induced (n=13), non-steroidal anti-inflammatory drug (NSAID)-enhanced (n=18), autoimmune (n=11), lymphocytic gastritis (n=26) and H. pylori-negative controls (n=17). The intensity of the staining was semiquantitatively analysed using an immunoreactivity score. Statistical analysis of differences was performed using an analysis of variance test. RESULTS: In comparison with the control group, the SLPI expression of antral mucosa in H. pylori-mediated and lymphocytic gastritis was significantly lower (P<0.001), whereas epithelial SLPI expression was not affected in NSAID-enhanced and autoimmune gastritis either in the antrum or corpus, respectively. Both the H. pylori-mediated and lymphocytic gastritis revealed a significantly lower expression of SLPI in infiltrating immune cells (P<0.01), whereas immune cells infiltrating the corpus in autoimmune gastritis showed higher SLPI levels than the immune cells of other groups (P<0.03). CONCLUSION: The local downregulation of SLPI in antral mucosa is specifically linked to H. pylori infection and is not a general phenomenon of gastric inflammation.

Adult↗

PubMed2005

Immune cell infiltration, cytokine expression, and beta-cell apoptosis during the development of type 1 diabetes in the spontaneously diabetic LEW.1AR1/Ztm-iddm rat.

The IDDM (LEW.1AR1/Ztm-iddm) rat is a type 1 diabetic animal model characterized by a rapid apoptotic pancreatic beta-cell destruction. Here we have analyzed the time course of islet infiltration, changes in the cytokine expression pattern, and beta-cell apoptosis in the transition from the pre-diabetic to the diabetic state. Transition from normoglycemia to hyperglycemia occurred when beta-cell loss exceeded 60-70%. At the early stages of islet infiltration, macrophages were the predominant immune cell type in the peripherally infiltrated islets. Progression of beta-cell loss was closely linked to a severe infiltration of the whole islet by CD8+ T-cells. With progressive islet infiltration, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were expressed in immune cells but not in beta-cells. This proinflammatory cytokine expression pattern coincided with the expression of inducible nitric oxide synthase (iNOS) and procaspase 3 in beta-cells and a peak apoptosis rate of 6.7%. Islet infiltration declined after manifestation of clinical diabetes, yielding end-stage islets devoid of beta-cells and immune cells without any sign of cytokine expression. The observed coincidence of IL-1beta and TNF-alpha expression in the immune cells and the induction of iNOS and procaspase 3 mRNA expression in the beta-cells depicts a sequence of pathological changes leading to apoptotic beta-cell death in the IDDM rat. This chain of events provides a mechanistic explanation for the development of the diabetic syndrome in this animal model of human type 1 diabetes.

Animals↗

PubMed2026

Immune-Like Malignant Epithelial Programs Shape Tumor-Immune Interactions and Inform Prognostic Stratification in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is characterized by marked cellular heterogeneity, yet how malignant epithelial states contribute to immune regulation and clinical outcomes remains incompletely defined. We integrated single-cell RNA-sequencing data to map the cellular landscape of LUAD and identify malignant epithelial cells based on inferred copy-number alterations. Epithelial states were further examined through trajectory inference, transcription factor analysis, and cell-cell communication profiling. Single-cell-derived genes were subsequently integrated with TCGA and independent GEO cohorts to construct and validate a machine learning-based prognostic signature. Malignant epithelial cells displayed distinct functional programs, including an immune-like state associated with genomic instability, immune-related transcriptional activity, tumor-immune communication, and patient outcomes. The resulting immune-like malignant epithelial cell signature (IMEC-Sig) consistently stratified survival across multiple cohorts. Low IMEC-Sig scores were accompanied by greater immune infiltration, higher immune checkpoint expression, and increased immunophenoscore, whereas high scores were linked to a comparatively immunosuppressive phenotype. Pan-cancer analyses further identified KRT8 as a gene associated with unfavorable prognosis, and functional experiments showed that KRT8 silencing suppressed proliferation, migration, invasion, and colony formation in LUAD cells. Together, these findings connect malignant epithelial heterogeneity with the immune context and clinical outcomes, support IMEC-Sig as a biologically informed prognostic tool, and nominate KRT8 as a potential therapeutic target in LUAD.

Humans↗

PubMed2026

Differences between mitotically old and young endometrial tumors.

Human tumors likely differ in their mitotic ages, reflecting how many divisions elapse between the final tumor progenitor cell and surgical removal. We used a rapidly fluctuating CpG (fCpG) methylation clock to infer relative endometrial adenocarcinomas (EAC) mitotic ages. Experimentally, young tumors initiated from single cells show low-diversity, high-variance fCpG distributions with trimodal peaks near 0%, 50%, and 100%, reflecting inherited progenitor methylation states. fCpG methylation becomes polymorphic with divisions, and older tumors exhibit higher diversity, lower variance, and unimodal distributions centered around 50%. Mitotic ages varied across EAC samples. Synchronous hyperplasia and invasive regions generally shared similar ages, and primary-metastatic EAC pairs showed both synchronous and stepwise progression. The Cancer Genome Atlas (TCGA) EACs also showed variable mitotic ages: younger tumors were enriched for proliferation pathways, whereas older tumors showed more immune infiltration, immune-pathway activation, and evidence of T-cell exhaustion. These results show that human tumors can be ranked by mitotic age and suggest that the growth of older cancers is restrained by immune surveillance. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Humans↗

PubMed2025

Notch pathway defines an aggressive and immune-suppressive phenotype associated with checkpoint inhibitor resistance in pan-gastrointestinal adenocarcinomas.

The Notch pathway regulates the homeostasis and tumorigenesis of gastrointestinal epithelium. Given its roles in cancer stem cell capacity and cancer immunity, we hypothesized that Notch activation can predict poor prognosis and resistance to immune checkpoint inhibitors (ICIs) in gastrointestinal adenocarcinoma (GIAC). The mRNA expression and genomic alterations of Notch pathway were characterized in esophagus (ESAD), stomach (STAD), colon (COAD), or rectum (READ) adenocarcinomas from The Cancer Genome Atlas (TCGA) dataset. The prognostic model (mRNA-score) was constructed using the TCGA dataset (the training set) and was validated in 3 independent sets (GSE19417 [ESAD], GSE84437 [STAD], and GSE40967 [COAD]). The associations of the mRNA-score with drug sensitivity, immune cell infiltration, and immunotherapy efficacy were, respectively, analyzed using the Genomics of Drug Sensitivity in Cancer (GDSC) database, the TCGA dataset, and multiple clinical cohorts including GSE165252, PRJEB25780, IMvigor210, and CheckMate-009/010/025. Notch pathway genes exhibited conserved genomic/transcriptomic features across four GIAC subtypes. Three pan-GIAC clusters were determined by unsupervised clustering, and the cluster with higher expression of the Notch pathway genes had shorter overall survival (OS), immunosuppressive microenvironment, and higher scores of the signatures concerning angiogenesis, cell cycle, PI3K-AKT-mTOR, TGF-β, glycolysis, etc. A prognostic algorithm (mRNA-score) was constructed, which was correlated with poor OS in the training set (TCGA, P < 0.001) and three validation sets (GSE19417, P = 0.025; GSE84437, P = 0.001, GSE40967, P = 0.007). A high mRNA-score was linked with more "resting"/ "anti-inflammatory" rather than "activated"/ "pro-inflammatory" tumor-infiltrating immune cells and ICI resistance in GIACs (GSE165252, P = 0.047; PRJEB25780, P = 0.047) and other solid tumors such as urothelial carcinoma and clear cell renal cell carcinoma. Our findings demonstrate the utility of the Notch pathway in predicting prognosis and ICI resistance. Further studies are warranted to explore the efficacy of Notch inhibitors as immunotherapeutic adjuvants to overcome ICI resistance.

Humans↗

PubMed1984

Interstitial and glomerular immune cell populations in idiopathic nephrotic syndrome.

Tissue samples from patients with idiopathic nephrotic syndrome [seven with minimal change (MC) and seven with mesangial proliferation (MP)] were examined for evidence of interstitial and glomerular immune cell infiltration using monoclonal antibodies to identify T cells (OKT3, TA-1), T cell subsets (OKT4, OKT8), B cells (BA-1), and monocytes and null cells (OKM1) by indirect immunofluorescence. A nuclear counterstain permitted precise enumeration of reactive and unreactive cells in comparison with five normal tissue samples, eight endstage (ES) tissue samples, and five tissue samples from patients with miscellaneous ( misc ) types of nephrotic syndrome. Interstitial cell populations in MC and MP were similar to normals except for an increase in OKM1 reactive cells in MP. ES had more numerous interstitial cells reactive with each of the monoclonal antibodies than did normal, MC, or MP. Reactive glomerular cells were most numerous in MP, intermediate in MC but only rarely observed in normal tissue samples. Most identifiable glomerular cells reacted with OKT3 or OKM1. T-cell subset populations in MC and MP glomeruli were similar. These studies reveal the presence of infiltrating immune cells in the glomeruli but not the renal interstitium of patients with idiopathic nephrotic syndrome. Whether these cells mediate proteinuria or simply mark tissue injury remains to be discerned.

Adolescent↗

PubMedDate not supplied

Immune cell infiltration and broncovascular remodeling after nitric acid nasal instillation in a mouse bronchiolitis obliterans model.

Immune cell airway infiltration and the bronchovascular remodeling process have shown to be promising in the understanding of bronchiolitis obliterans (BO) pathogenesis. In this study we sought to validate the importance of immune cells, whether diffusely distributed or forming lymphoid follicles, collagen density, and vascular factors. Eight weeks after a single nitric acid (NA) nasal instillation, lung changes were characterized by lumen distortion, epithelial layer folding, reduction or total obliteration of terminal bronchiole (TB) lumen, and wall thickness increase. The morphologic changes in the TB and TA (terminal artery) lumen coincide with the measurement difference in the three groups. The TB diameter and lumen were significantly decreased in BO when compared with non-BO lungs (0.76 +/- 0.05 microm vs. 0.81 +/- 0.05 microm and 12,286.13 +/- 378.83 microm vs. 18,182.27 +/- 5,593.98 microm, p = 0.05 and p = 0.01, respectively). Equally significant was the increase in TB thickness in BO when compared with the non-BO group (201.72 +/- 35.75 microm vs. 149.75 +/- 40.61 microm, p = 0.007). The morphologic changes in immune cells seen in TB, TA, and bronchus-associated lymphoid tissue (BALT) also coincide with the quantification differences observed in the three groups. We concluded that immune cell infiltration and collagen/vascular remodeling are related to the spectrum of histologic changes in a BO nasal-induced model in mice and may be an appropriate target for prospective studies of human bronchiolitis.

Administration, Intranasal↗

PubMed1991

Experimentally-induced autoimmune myocarditis: production of heart myosin-specific autoantibodies within the inflammatory infiltrate.

Immunization with cardiac myosin in complete Freund's adjuvant (CFA) induces severe autoimmune myocarditis in A H-2 congenic mouse strains. The disease shares a variety of characteristics with Coxsackie-virus B3 (CB3)-induced myocarditis and is strongly associated with high-titered autoantibodies to cardiac myosin. Using the spot ELISA-technique, we demonstrate here that in cardiac myosin-immunized mice myosin autoantibodies were not only produced within the spleen, but also at the site of the autoimmune attack, i.e., within the inflammatory heart infiltrate. At the level of single plasma cells we further showed that a substantial part of the myosin autoantibodies was specific for the cardiac myosin isoform, thereby supporting previous serologic data. The finding that cells of the inflammatory heart infiltrate significantly contribute to autoantibody production might explain why the occurrence of high-titered myosin autoantibodies is restricted to mice which develop the disease.

Animals↗

PubMed1997

Immune cell infiltration and growth-associated protein 43 expression correlate with pain in chronic pancreatitis.

BACKGROUND & AIMS: Changes in innervation pattern and neuropeptide content have been shown in chronic pancreatitis (CP), including increased neuronal expression of growth-associated protein 43 (GAP-43). We used GAP-43 as an established marker of neuronal plasticity and correlated histological findings with pain scores of patients with CP. METHODS: In tissue samples from 29 patients with CP, the parenchyma-fibrosis ratio, degree of perineural immune cell infiltration, and neuronal GAP-43 immunoreactivity were determined by digitized morphometry and correlated with individual pain scores. RESULTS: In CP, GAP-43 was significantly increased in pancreatic nerve fibers and intrinsic neurons. GAP-43 expression correlated with individual pain scores. The infiltration of pancreatic nerves by immune cells was significantly correlated with the intensity of pain. Pain scores correlated neither with the degree of pancreatic fibrosis nor with the duration of the disease. CONCLUSIONS: The results suggest that infiltration of pancreatic nerves by immune cells and neuronal plasticity are pathogenic factors for the generation of pain, whereas the degree of pancreatic fibrosis has no major impact on pain in CP.

Adolescent↗

PubMed2025

Experimental study on the role and biomarker potential of CX3CR1 in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disorder marked by progressive degeneration of articular cartilage and the formation of secondary osteophytes. Despite extensive research, the underlying molecular mechanisms remain poorly understood. This study aimed to identify OA-associated genes and elucidate the molecular pathways implicated, with the goal of discovering reliable diagnostic biomarkers. METHODS: The microarray dataset was retrieved from the Gene Expression Omnibus (GEO) and analyzed using R software to identify the signature gene, CX3CR1. Differentially expressed genes (DEGs) correlated with CX3CR1 were subsequently subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and immune infiltration analyses. A ceRNA regulatory network was also constructed. Vali-dation of CX3CR1 expression was conducted through qRT-PCR, Western blotting, and immunohistochemistry. RESULTS: CX3CR1 emerged as a candidate gene significantly associated with OA, exhibiting regulatory roles primarily in lipid metabolism-related and extra-cellular matrix-related biological processes and signaling cascades. The infiltration levels of immune cells, particularly activated mast cells, appeared to modulate OA progression. Both in vitro and in vivo experiments demonstrated elevated CX3CR1 expression in OA tissues relative to controls, with a robust positive correlation observed between CX3CR1 and MMP13 levels. CONCLUSION: CX3CR1 represents a potential biomarker for OA diagnosis and therapeutic targeting, exerting its effects by modulating lipid metabolism, extracellular matrix dynamics, and immune cell infiltration.

CX3C Chemokine Receptor 1↗

PubMed1986

[Studies on the interaction between trophoblastic invasion and maternal immune cell infiltration at the implantation site in early human pregnancy by means of double immunoperoxidase technic using monoclonal antibodies].

Interaction between trophoblastic invasion and maternal immune cell infiltration at the implantation sites in early human pregnancy was analyzed by means of a double immunoperoxidase technique using Troma-1, a rat monoclonal antibody, which recognizes trophoblastic cells and a set of mouse monoclonal antibodies to react with various immune cells. The results were as follows. The most prominent immune cells in the implantation sites were monocytes/macrophages, which were positive for HLA-DR. These cells were adjacent to trophoblastic cells which were infiltrating into the decidua basalis. It therefore appeared that these cells function as "antigen presenting cells" which recognize and present the processed fetal information to maternal T cells. A small number of cells with mature T cell markers were found to be infiltrating around the anchoring villi and the extra-villous trophoblastic cells in the decidua compacta. But a larger number of T cells were adjacent to the villi in the decidua spongiosa and the extra-villous trophoblastic cells invading the decidua spongiosa and the myometrium. These cells may therefore play a role in preventing trophoblastic cells from invading the myometrium in the implantation sites. A relatively large number of cells with E rosette receptors but without mature T cell markers were observed in the decidua basalis, but few were found in the myometrium, into which a larger number of mature T cells were infiltrating. The distribution of particular cells was similar to that of endometrial granulocytes studied in our laboratory. There were thus likely to be immune cells in humans equivalent to non-T granulated suppressor cells in mice, which have been shown to suppress the generation of cytotoxic T cells (Clark et al.).

Antibodies, Monoclonal↗