scholarly journals Functionally Mature CD1c+ Dendritic Cells Preferentially Accumulate in the Inflammatory Arthritis Synovium

2021 ◽  
Vol 12 ◽  
Author(s):  
Mary Canavan ◽  
Viviana Marzaioli ◽  
Vipul Bhargava ◽  
Sunil Nagpal ◽  
Phil Gallagher ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Synovial Tissue ◽  
Inflammatory Arthritis ◽  
Antigen Processing ◽  
Expression Patterns ◽  
Multiparametric Flow Cytometry ◽  
Transcriptional Variation ◽  
Healthy Control ◽  
Dc Maturation

ObjectiveTo examine the role of synovial CD1c+DCs in patients with Inflammatory Arthritis (IA) with a specific focus on the transcriptional and maturation signatures that govern their function.MethodsRNA sequencing was performed on healthy control (HC) peripheral blood (PB), IA PB, and IA synovial fluid (SF) CD1c+DCs. Multiparametric flow-cytometry and SPICE analysis were used to examine site [SF and Synovial Tissue (ST) CD1c+DCs] and disease specific characteristics of CD1c+DCs, while functional assays such as antigen processing, activation, and MMP production were also performed.ResultsIncreased frequency of CD1c+DCs (p<0.01) with a concomitant increase in CD80, CCR7 (p<0.01), and CXCR3 (p<0.05) expression was identified in IA PB compared to HC PB. Enrichment of CD1c+DCs was identified in IA synovial tissue (ST) (p<0.01) and IA SF (p<0.0001) compared to IA PB, while RNAseq revealed distinct transcriptional variation between PB and SF CD1c+DCs. Flow cytometry revealed increased expression of CD83, CD80, PD-L1, and BTLA (all p<0.05) in IA SF CD1c+DCs compared to PB, while SPICE identified synovial cells with unique co-expression patterns, expressing multiple DC maturation markers simultaneously. Functionally, synovial CD1c+DCs are hyper-responsive to TLR7/8 ligation (p<0.05), have decreased antigen processing capacity (p=0.07), and display dysregulated production of MMPs. Finally, examination of both synovial CD1c+DCs and synovial CD141+DCs revealed distinct maturation and transcriptomic profiles.ConclusionSynovial CD1c+DCs accumulate in the inflamed IA synovium in a variety of distinct poly-maturational states, distinguishing them transcriptionally and functionally from CD1c+DCs in the periphery and synovial CD141+DCs.

scholarly journals Primary role of multiparametric flow cytometry in the diagnostic work-up of indolent clonal mast cell disorders

2011 ◽  
Vol 80B (6) ◽  
pp. 362-368 ◽  
Author(s):  
Omar Perbellini ◽  
Alberto Zamò ◽  
Sabrina Colarossi ◽  
Francesca Zampieri ◽  
Francesca Zoppi ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Mast Cell ◽  
Primary Role ◽  
Multiparametric Flow Cytometry ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up

scholarly journals INFLAMMATION AND IMMUNITY: A ROLE OF PATHOGENESIS OF OSTEOARTHRITIS

2019 ◽  
Vol 21 (1) ◽  
pp. 39-48 ◽  
Author(s):  
V. S. Shirinsky ◽  
E. V. Kazygasheva ◽  
I. V. Shirinsky
Keyword(s):  
Immune Response ◽  
Synovial Tissue ◽  
Subchondral Bone ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Healthy Control ◽  
Anti Inflammatory ◽  
Clinically Significant

In this review we analyze literature data concerning participation of synovial inflammation, subchondral bone, humoral and cellular immune responses towards various cartilage autoantigens in the initiation and progression of primary osteoarthritis (OA). The vast majority of studies showed that the synovial inaflammation in OA is less pronounced than in RA but is more pronounced than in healthy people. In OA synovial tissue, macrophages and T-cells predominate in the inflammatory infiltrate. Some authors detected mast cells in the OA synovium in quantities higher than in healthy control and significantly higher than in RA patients. Most of researchers found many cytokines related to innate and adaptive immune cells in the OA synovial tissue, while in some studies the cells producing those cytokines were not identified. Among the cytokines there were both pro-inflammatory and anti-inflammatory ones: IL-1b, TNFα, IFNγ, IL-4, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18. In addition, some authors detected IL-5, IL-13, IL-19, IL-21, IL-26, IL-32, and TGFb. A role of adaptive immune response in OA is supported by the presence of autoantibodies against antigen determinants of collagens type II, IX, XI, aggrecan, fibronectin fragments, in the synovial tissue, synovium fluid, and peripheral blood serum. The research data clearly support a role of chronic inflammation and changes in innate and adaptive immune response in the pathogenesis of OA thus justifying the change of the disease name from “osteoarthrosis” to “osteoarthritis”. This novel understanding of OA pathogenesis is paramount as it provides a rationale for modern anti-inflammatory treatments and discovery of new therapeutic targets. We discuss the results of studies evaluating efficacy and safety of some types of anti-inflammatory treatment of OA. Until now, treatment of OA directed on inflammation control was not successful. Thus, clinical trials of anti-TNFα anti-IL-1b strategies for the treatment of OA did not show clinically significant improvement in spite of multiple studies demonstrating elevated concentrations of TNFα and IL-1bin synovial fluid and subchondral bone in OA thus suggesting the role of these cytokines in the OA pathogenesis. On the other side, treatment with IL-1 inhibitor diacerein was found to be effective which can be explained by pleiotropic effects of this drug. It should be stressed out that in order to increase the efficacy of anti-inflammatory treatments of OA they should be initiated at early disease stages, thus necessitating the use of new informative biormarkers of early OA.

Dysregulation of HOX as a Potential Therapeutic Target in Breast Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ji-Yeon Lee ◽  
Myoung Hee Kim
Keyword(s):  
Breast Cancer ◽  
Hox Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Genome Structure ◽  
Control Cell ◽  
Three Dimensional ◽  
Cellular Processes ◽  
Hox Protein

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

scholarly journals Exosomes from human umbilical cord mesenchymal stem cells attenuate the inflammation of severe steroid-resistant asthma by reshaping macrophage polarization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bing Dong ◽  
Chao Wang ◽  
Jing Zhang ◽  
Jinrong Zhang ◽  
Yinuo Gu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Quantitative Proteomics ◽  
Macrophage Polarization ◽  
Human Umbilical Cord ◽  
Raw 264.7 ◽  
Steroid Resistant ◽  
Central Protein

Abstract Background Severe, steroid-resistant asthma (SSRA) is a serious clinical problem in asthma management. Affected patients have severe clinical symptoms, worsened quality of life, and do not respond to steroid, a mainstay steroid treatment of asthma. Thus, effective therapies are urgently needed. Exosomes derived from mesenchymal stem cell (MSC-Exo) has become attractive candidates for the lung inflammatory diseases through its immunomodulatory effects. In this study, we explored the therapeutic effects of MSC-Exo in SSRA and identified the therapeutic mechanism of MSC-Exo. Method Exosomes from human umbilical cord mesenchymal stem cell (hUCMSC) were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis and flow cytometry analysis. Effects of MSC-Exo on airway hyper responsiveness (AHR), inflammation, histopathology, and macrophage polarization in SSRA in mice were evaluated. Systematic depletion of macrophages determined the role of macrophages in the therapeutic effect of SSRA in mice. LPS-stimulated RAW 264.7 cell model was constructed to determine the underlying mechanism of MSC-Exo on macrophage polarization. qRT-PCR, Western blotting, immunofluorescence, and flow cytometry were performed to evaluate the expression of M1 or M2 markers. Tandem mass tags (TMT)-labeled quantitative proteomics were applied to explore the central protein during the regulation effect of MSC-Exo on macrophage polarization. Knockdown and overexpression of TRAF1 were used to further clarify the role of the central protein on macrophage polarization. Result We successfully isolated and characterized exosomes from hUCMSCs. We verified that the intratracheal administration of MSC-Exo reversed AHR, histopathology changes, and inflammation in SSRA mice. Systematic depletion of macrophages weakened the therapeutic effect of MSC-Exo. We found that MSC-Exo treatment inhibited M1 polarization and promoted M2 polarization in LPS-stimulated RAW 264.7 cells. Subsequently, tumor necrosis factor receptor-associated factor 1 (TRAF1) was determined as the central protein which may be closely related to the regulation of macrophage polarization from TMT-labeled quantitative proteomics analysis. Knockdown and overexpression of TRAF1 demonstrated that the effect of MSC-Exo treatment on macrophage polarization, NF-κB and PI3K/AKT signaling was dependent on TRAF1. Conclusion MSC-Exo can ameliorate SSRA by moderating inflammation, which is achieved by reshaping macrophage polarization via inhibition of TRAF1.

scholarly journals Evaluation of the role of CD47 in sickle cell disease

2021 ◽  
Author(s):  
Basmah Eldakhakhny ◽  
Hadeel Al Sadoun ◽  
Nehal Bin Taleb ◽  
Dunya Ahmed Nori ◽  
Nawal Helmi ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Annexin V ◽  
Cell Disease ◽  
Phagocytic Cells ◽  
Surface Marker Expression ◽  
Inflammatory Phenotype ◽  
Healthy Control ◽  
Cell Surface Marker Expression ◽  
Pro Inflammatory Cytokines

AbstractCD47 is a self-marker expressed on the surface of RBCs and work to prevent the process of phagocytosis. SIRPα is the ligand of CD47 that is expressed on the surface of phagocytic cells, such as macrophages, to control the removal of dead/diseased cells. This study aimed to examine the expression of CD47 on RBCs and SIRPα on PBMC cells in SCD patients and the apoptosis of SCD RBCs. We also measured the levels of pro-inflammatory cytokines in SCD patients and correlated it with the cell surface marker expression of CD47 and SIRPα to determine whether CD47 and/or SIRPα played a role in promoting the pro-inflammatory phenotype in SCD. Whole blood samples were drawn from SCD patients, and healthy control and PBMC were isolated and stained with SIRPα. Change in CD47, apoptosis by annexin V marker, and pro-inflammatory cytokines were measured and correlation among these variants was determined. The expression of CD47 was significantly decreased and the apoptosis was increased in RBCs of SCD patients. A higher level of pro-inflammatory cytokines, IL-6 and IL-1β, was found in SCD patients and IL-1β was found to be inversely correlated with SIRPα expression. Our data showed that CD47 of erythrocytes of SCD samples is reduced and that the apoptosis is increased in those patients. Based on the role of CD47, we suggest that increased apoptosis in SCD would be impacted by the reduced level of CD47. An inverse relationship was found between SIRPα marker on PBMC and the increased production of pro-inflammatory cytokines in SCD.

scholarly journals VEGF as a potential molecular target in periodontitis: a meta-analysis and microarray data validation

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Bo Ren ◽  
Que Feng ◽  
Shan He ◽  
Yanfeng Li ◽  
Jiadong Fan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Clinical Sample ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Therapeutic Drug ◽  
Data Validation ◽  
Control Groups ◽  
Vegf Expression ◽  
Healthy Control

Abstract Background Anti-vascular endothelial growth factor (VEGF) has been used as a therapeutic drug for the treatment of some human diseases. However, no systematic evidence is performed for assessing the role of VEGF in periodontitis. We carried out a comprehensive analysis to explore the role of VEGF in patients with periodontitis. Methods Multiple databases were searched for eligible studies. The pooled standardized mean difference (SMD) and odds ratio (OR) with the corresponding 95% confidence interval (CI) were applied to evaluate the effect sizes. Clinical data validation from microarray analysis was used. Pathway and process enrichment analysis were also investigated. Results Finally, 16 studies were included in this analysis. Overall, there was a significantly higher level of VEGF expression in periodontitis than in healthy control groups (OR = 16.64, 95% CI = 6.01–46.06, P < 0.001; SMD = 2.25, 95% CI = 1.25–3.24, P < 0.001). Subgroup analysis of ethnicity showed that VEGF expression was still correlated with periodontitis in the Asian and European populations. No correlation was observed between VEGF expression and age, gender, and pathological type. A large clinical sample data (427 periodontitis patients and 136 healthy controls) further validated that VEGF expression was higher in periodontitis than in healthy control groups (P = 0.023). VEGF was involved in many functions such as blood vessel development, response to growth factor, cell proliferation, and cell adhesion. Conclusions High levels of VEGF were credible implications for the development of periodontitis. Anti-VEGF therapy may be valuable for the treatment of periodontitis in clinical management.

scholarly journals The potential regulatory role of hsa_circ_0004104 in the persistency of atrial fibrillation by promoting cardiac fibrosis via TGF-β pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuanfeng Gao ◽  
Ye Liu ◽  
Yuan Fu ◽  
Qianhui Wang ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Expression Patterns ◽  
In Silico Analysis ◽  
Significant Negative Correlation ◽  
Circular Rnas ◽  
Tgf Beta ◽  
Rt Pcr ◽  
Derivation Cohort ◽  
Tgf Β1

Abstract Introduction The progression of paroxysmal AF (PAF) to persistent AF (PsAF) worsens the prognosis of AF, but its underlying mechanisms remain elusive. Recently, circular RNAs (circRNAs) were reported to be associated with cardiac fibrosis. In case of the vital role of cardiac fibrosis in AF persistency, we hypothesis that circRNAs may be potential regulators in the process of AF progression. Materials and methods 6 persistent and 6 paroxysmal AF patients were enrolled as derivation cohort. Plasma circRNAs expressions were determined by microarray and validated by RT-PCR. Fibrosis level, manifested by serum TGF-β, was determined by ELISA. Pathways and related non-coding RNAs involving in the progression of AF regulated were predicted by in silico analysis. Results PsAF patients showed a distinct circRNAs expression profile with 92 circRNAs significantly dysregulated (fold change ≥ 2, p < 0.05), compared with PAF patients. The validity of the expression patterns was subsequently validated by RT-PCR in another 60 AF patients (30 PsAF and PAF, respectively). In addition, all the 5 up and down regulated circRNAs were clustered in MAPK and TGF-beta signaling pathway by KEGG pathway analysis. Among the 5 circRNAs, hsa_circ_0004104 was consistently downregulated in PsAF group (0.6 ± 0.33 vs 1.46 ± 0.41, p < 0.001) and predicted to target several AF and/or cardiac fibrosis related miRNAs reported by previous studies. In addition, TGF-β1 level was significantly higher in the PsAF group (5560.23 ± 1833.64 vs 2236.66 ± 914.89, p < 0.001), and hsa_circ_0004104 showed a significant negative correlation with TGF-β1 level (r = − 0.797, p < 0.001). Conclusion CircRNAs dysregulation plays vital roles in AF persistency. hsa_circ_0004104 could be a potential regulator and biomarker in AF persistency by promoting cardiac fibrosis via targeting MAPK and TGF-beta pathways.

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