Developmental stage-specific differential expression of non-coding RNAs in mammalian gamma delta T-cells.

2019 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Microarray Dataset ◽  
Differentially Expressed ◽  
Gamma Delta T Cells ◽  
Small Nuclear Rna ◽  
Gamma Delta ◽  
Lineage Specification ◽  
Non Coding Rna ◽  
Non Coding Rnas

Gamma delta T-cells, 𝛄δ T-cells or T𝛄δ reside in the blood and in tissues, functioning in both innate and adaptive roles (1). We performed global differential gene expression analysis of embryonic and adult gamma T𝛄δ from mice using a published microarray dataset (2). We found that a series of non-coding RNA transcripts were among the most differentially expressed genes when comparing embryonic and adult T𝛄δ. These transcripts included long non-coding RNA, pseudogenes, a small nuclear RNA and an antisense transcript. The fact that multiple non-coding RNAs are differentially expressed in a stage-selective manner in T𝛄δ suggests that they serve some vital developmental function, in the repression, activation, or integration of gene expression programs critical for T𝛄δ lineage specification or effector function.

scholarly journals Construction of asthma related competing endogenous RNA network revealed novel long non-coding RNAs and potential new drugs

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yifang Liao ◽  
Ping Li ◽  
Yanxia Wang ◽  
Hong Chen ◽  
Shangwei Ning ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Repositioning ◽  
New Drugs ◽  
Differentially Expressed ◽  
Interaction Data ◽  
Competing Endogenous Rna ◽  
Non Coding Rna ◽  
Competing Endogenous Rna Network ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Abstract Background Asthma is a heterogeneous disease characterized by chronic airway inflammation. Long non-coding RNA can act as competing endogenous RNA to mRNA, and play significant role in many diseases. However, there is little known about the profiles of long non-coding RNA and the long non-coding RNA related competing endogenous RNA network in asthma. In current study, we aimed to explore the long non-coding RNA-microRNA-mRNA competing endogenous RNA network in asthma and their potential implications for therapy and prognosis. Methods Asthma-related gene expression profiles were downloaded from the Gene Expression Omnibus database, re-annotated with these genes and identified for asthma-associated differentially expressed mRNAs and long non-coding RNAs. The long non-coding RNA-miRNA interaction data and mRNA-miRNA interaction data were downloaded using the starBase database to construct a long non-coding RNA-miRNA-mRNA global competing endogenous RNA network and extract asthma-related differentially expressed competing endogenous RNA network. Finally, functional enrichment analysis and drug repositioning of asthma-associated differentially expressed competing endogenous RNA networks were performed to further identify key long non-coding RNAs and potential therapeutics associated with asthma. Results This study constructed an asthma-associated competing endogenous RNA network, determined 5 key long non-coding RNAs (MALAT1, MIR17HG, CASC2, MAGI2-AS3, DAPK1-IT1) and identified 8 potential new drugs (Tamoxifen, Ruxolitinib, Tretinoin, Quercetin, Dasatinib, Levocarnitine, Niflumic Acid, Glyburide). Conclusions The results suggested that long non-coding RNA played an important role in asthma, and these novel long non-coding RNAs could be potential therapeutic target and prognostic biomarkers. At the same time, potential new drugs for asthma treatment have been discovered through drug repositioning techniques, providing a new direction for the treatment of asthma.

scholarly journals Novel Immune-Related Genetic Expression for Primary Sjögren's Syndrome

2022 ◽  
Vol 8 ◽  
Author(s):  
Jiajia Cui ◽  
Hui Li ◽  
Tianling Wang ◽  
Qin Shen ◽  
Yuanhao Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Primary Sjögren’S Syndrome ◽  
Memory B Cells ◽  
Gamma Delta T Cells ◽  
Ppi Network ◽  
Gamma Delta ◽  
Key Genes

Objective: To identify novel immune-related genes expressed in primary Sjögren's syndrome (pSS).Methods: Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were screened. The differences in immune cell proportion between normal and diseased tissues were compared, weighted gene co-expression network analysis was conducted to identify key modules, followed by a protein–protein interaction (PPI) network generation and enrichment analysis. The feature genes were screened and verified using the GEO datasets and quantitative real-time PCR (RT-qPCR).Results: A total of 345 DEGs were identified, and the proportions of gamma delta T cells, memory B cells, regulatory T cells (Tregs), and activated dendritic cells differed significantly between the control and pSS groups. The turquoise module indicated the highest correlation with pSS, and 252 key genes were identified. The PPI network of key genes showed that RPL9, RBX1, and RPL31 had a relatively higher degree. In addition, the key genes were mainly enriched in coronavirus disease-COVID-2019, hepatitis C, and influenza A. Fourteen feature genes were obtained using the support vector machine model, and two subtypes were identified. The genes in the two subtypes were mainly enriched in the JAK-STAT, p53, and toll-like receptor signaling pathways. The majority of the feature genes were upregulated in the pSS group, verified using the GEO datasets and RT-qPCR analysis.Conclusions: Memory B cells, gamma delta T cells, Tregs, activated dendritic cells, RPL9, RBX1, RPL31, and the feature genes possible play vital roles in the development of pSS.

scholarly journals A gene expression-based study on immune cell subtypes and glioma prognosis

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiu-Yue Zhong ◽  
Er-Xi Fan ◽  
Guang-Yong Feng ◽  
Qi-Ying Chen ◽  
Xiao-Xia Gou ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Data Analysis ◽  
Nk Cells ◽  
Immune Cells ◽  
Prognostic Value ◽  
Immune Cell ◽  
High Morbidity ◽  
Gamma Delta T Cells ◽  
Gamma Delta

Abstract Object Glioma is a common malignant tumours in the central nervous system (CNS), that exhibits high morbidity, a low cure rate, and a high recurrence rate. Currently, immune cells are increasingly known to play roles in the suppression of tumourigenesis, progression and tumour growth in many tumours. Therefore, given this increasing evidence, we explored the levels of some immune cell genes for predicting the prognosis of patients with glioma. Methods We extracted glioma data from The Cancer Genome Atlas (TCGA). Using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, the relative proportions of 22 types of infiltrating immune cells were determined. In addition, the relationships between the scales of some immune cells and sex/age were also calculated by a series of analyses. A P-value was derived for the deconvolution of each sample, providing credibility for the data analysis (P < 0.05). All analyses were conducted using R version 3.5.2. Five-year overall survival (OS) also showed the effectiveness and prognostic value of each proportion of immune cells in glioma; a bar plot, correlation-based heatmap (corheatmap), and heatmap were used to represent the proportions of immune cells in each glioma sample. Results In total, 703 transcriptomes from a clinical dataset of glioma patients were drawn from the TCGA database. The relative proportions of 22 types of infiltrating immune cells are presented in a bar plot and heatmap. In addition, we identified the levels of immune cells related to prognosis in patients with glioma. Activated dendritic cells (DCs), eosinophils, activated mast cells, monocytes and activated natural killer (NK) cells were positively related to prognosis in the patients with glioma; however, resting NK cells, CD8+ T cells, T follicular helper cells, gamma delta T cells and M0 macrophages were negatively related to prognosis in the patients with glioma. Specifically, the proportions of several immune cells were significantly related to patient age and sex. Furthermore, the level of M0 macrophages was significant in regard to interactions with other immune cells, including monocytes and gamma delta T cells, in glioma tissues through sample data analysis. Conclusion We performed a novel gene expression-based study of the levels of immune cell subtypes and prognosis in glioma, which has potential clinical prognostic value for patients with glioma.

scholarly journals Coding and non-coding RNAs transcribed at the RORA locus (ROR𝛂) are differentially expressed in the whole blood of sepsis patients.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Expression Analysis ◽  
Whole Blood ◽  
Gene Expression Analysis ◽  
Differentially Expressed ◽  
Blood Gene Expression ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Sepsis is a leading cause of mortality (1). We mined published datasets from the whole blood of patients with sepsis to identify differentially expressed genes in the septic state (2, 3). We found changes in RORA expression as among the most significant quantitative differences in sepsis whole blood gene expression. Analysis of a separate dataset (4) demonstrated significant repression of a long non-coding RNA produced at the RORA locus in the blood of patients with sepsis.

scholarly journals UNIQUE TRANSCRIPTOME OF AGE-ASSOCIATED VISCERAL FAT-RESIDENT GAMMA DELTA T CELLS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S964-S964
Author(s):  
Marlene E Starr
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Visceral Fat ◽  
Cell Function ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Age Related ◽  
Age Dependent ◽  
High Representation

Abstract Gamma delta T cells (Tγδ) are a unique group of immune cells that perform both adaptive and innate functions. We recently identified a population of Tγδ cells which show an age-dependent expansion in the visceral fat of both mice and humans. However, little is known regarding the role of these cells in the fat. The purpose of this study was to begin delineating their role by: (1) comparing the gene expression profile of visceral fat-resident Tγδ to conventional T cells (Tconv) and to circulating Tγδ, and (2) identifying age-dependent changes in gene expression within the visceral fat-resident Tγδ population. Tγδ and Tconv were magnetically purified from blood and visceral fat of young and aged mice. Using NanoString technology, we found that overall transcriptomes of Tγδ in fat and blood were strikingly different. Transcriptomes of Tγδ and Tconv within the fat were more similar, but distinct with the former having high representation of pathways related to inflammation, cytokine and chemokine signaling, and macrophage function and the latter having high representation of pathways related to T- and B-cell function and TNF superfamily. Within the Tγδ population we identified significant (&gt;1.8-fold change, p&lt;0.01) age-associated differences in expression for 8 upregulated genes (C6, Cxcl13, Prg2, Il5ra, Ctla4, Marco, Ccl8, Il10) and 10 downregulated genes (Col4a1, Xcl1, Col1a1, Cfd, Col3a1, Lbp, Thbs1, Klrd1, Il6st, Ccl17). These genes will guide further research aimed at understanding the role of these cells and how their age-associated changes contribute to chronic inflammation, an underlying component of multiple age-related diseases.

Anti-Tumor Actions of Trametes Versicolor Extract Polysaccharide K Include Activation of Dendritic Cells and Gamma Delta T Cells

Planta Medica ◽  
2013 ◽  
Vol 79 (10) ◽  
Author(s):  
CA Wenner ◽  
C Inatsuka ◽  
T Davis Smith ◽  
M Sasagawa ◽  
MR Martzen ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Trametes Versicolor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Polysaccharide K

scholarly journals OP0021 IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN EARLY RHEUMATOID ARTHRITIS PATIENTS RESPONDING TO TOCILIZUMAB

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 12.2-12
Author(s):  
I. Muller ◽  
M. Verhoeven ◽  
H. Gosselt ◽  
M. Lin ◽  
T. De Jong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
T Cells ◽  
Gene Ontology ◽  
Regulatory T Cells ◽  
Early Rheumatoid Arthritis ◽  
Whole Blood ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Double Blind

Background:Tocilizumab (TCZ) is a monoclonal antibody that binds to the interleukin 6 receptor (IL-6R), inhibiting IL-6R signal transduction to downstream inflammatory mediators. TCZ has shown to be effective as monotherapy in early rheumatoid arthritis (RA) patients (1). However, approximately one third of patients inadequately respond to therapy and the biological mechanisms underlying lack of efficacy for TCZ remain elusive (1). Here we report gene expression differences, in both whole blood and peripheral blood mononuclear cells (PBMC) RNA samples between early RA patients, categorized by clinical TCZ response (reaching DAS28 < 3.2 at 6 months). These findings could lead to identification of predictive biomarkers for TCZ response and improve RA treatment strategies.Objectives:To identify potential baseline gene expression markers for TCZ response in early RA patients using an RNA-sequencing approach.Methods:Two cohorts of RA patients were included and blood was collected at baseline, before initiating TCZ treatment (8 mg/kg every 4 weeks, intravenously). DAS28-ESR scores were calculated at baseline and clinical response to TCZ was defined as DAS28 < 3.2 at 6 months of treatment. In the first cohort (n=21 patients, previously treated with DMARDs), RNA-sequencing (RNA-seq) was performed on baseline whole blood PAXgene RNA (Illumina TruSeq mRNA Stranded) and differential gene expression (DGE) profiles were measured between responders (n=14) and non-responders (n=7). For external replication, in a second cohort (n=95 therapy-naïve patients receiving TCZ monotherapy), RNA-seq was conducted on baseline PBMC RNA (SMARTer Stranded Total RNA-Seq Kit, Takara Bio) from the 2-year, multicenter, double-blind, placebo-controlled, randomized U-Act-Early trial (ClinicalTrials.gov identifier: NCT01034137) and DGE was analyzed between 84 responders and 11 non-responders.Results:Whole blood DGE analysis showed two significantly higher expressed genes in TCZ non-responders (False Discovery Rate, FDR < 0.05): urotensin 2 (UTS2) and caveolin-1 (CAV1). Subsequent analysis of U-Act-Early PBMC DGE showed nine differentially expressed genes (FDR < 0.05) of which expression in clinical TCZ non-responders was significantly higher for eight genes (MTCOP12, ZNF774, UTS2, SLC4A1, FECH, IFIT1B, AHSP, and SPTB) and significantly lower for one gene (TND2P28M). Both analyses were corrected for baseline DAS28-ESR, age and gender. Expression of UTS2, with a proposed function in regulatory T-cells (2), was significantly higher in TCZ non-responders in both cohorts. Furthermore, gene ontology enrichment analysis revealed no distinct gene ontology or IL-6 related pathway(s) that were significantly different between TCZ-responders and non-responders.Conclusion:Several genes are differentially expressed at baseline between responders and non-responders to TCZ therapy at 6 months. Most notably, UTS2 expression is significantly higher in TCZ non-responders in both whole blood as well as PBMC cohorts. UTS2 could be a promising target for further analyses as a potential predictive biomarker for TCZ response in RA patients in combination with clinical parameters (3).References:[1]Bijlsma JWJ, Welsing PMJ, Woodworth TG, et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet. 2016;388(10042):343-55.[2]Bhairavabhotla R, Kim YC, Glass DD, et al. Transcriptome profiling of human FoxP3+ regulatory T cells. Human Immunology. 2016;77(2):201-13.[3]Gosselt HR, Verhoeven MMA, Bulatovic-Calasan M, et al. Complex machine-learning algorithms and multivariable logistic regression on par in the prediction of insufficient clinical response to methotrexate in rheumatoid arthritis. Journal of Personalized Medicine. 2021;11(1).Disclosure of Interests:None declared

600 In vitro anticancer and immunomodulatory activities of NBT-167, a dimer of resveratrol

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A635-A635
Author(s):  
Jeffrey Zhang ◽  
Everett Henry ◽  
L Harris Zhang ◽  
Wanying Zhang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Immune Cells ◽  
Cell Killing ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Raw264.7 Macrophages

BackgroundResveratrol (3,4’,5-trihydroxystilbene), a stilbenoid isolated from many species of plants, is widely known for its antioxidative, anti-inflammatory, immunomodulatory and anticancer activities. Recently, novel resveratrol oligomers have been isolated from various plants; their diverse structures are characterized by the polymerization of two or more resveratrol units. Little is known regarding the anticancer and immunomodulating activities of these oligomers. In this study, we designed in vitro models to compare resveratrol side by side with its natural dimer NBT-167 for their anticancer and immunological activities.MethodsWe isolated resveratrol and its dimer (NBT-167) from plants. The potency of the compounds was compared side by side using cancer cell survival assays and immunological assays with various types of human cells including cancer cell lines, PBMCs and enriched NK, gamma delta T cells, THP-1 monocytic cells, HL-60 promyelocytic leukemia cells as well as mouse RAW264.7 macrophages.ResultsNBT-167 was found to be more potent than resveratrol in inhibiting growth of various cancer cells and modulation of cytokine production from anti-IgM, LPS, PHA or SEB stimulated PBMC. Both compounds similarly enhanced IL-2 stimulated NK and gamma delta T cell killing activity against K562 cells and modulated nitric oxide production from LPS/IFN-g induced RAW264.7 macrophages and phagocytotic activity of HL-60 cells. NBT-167 was slightly more potently than resveratrol in inhibiting chemotaxis of HL-60 cells and blocking cell cycle of THP-1 and HL-60 cells at G1/S transition. In addition, NBT-167, but not resveratrol, could increase IL-2 production and T cell proliferation stimulated with anti-CD3 and anti-CD28 and synergize with anti-PD-1 antibody to increase IL-2 and IFN-gamma production in co-culture of allotypic T cells and dendric cells (MLR).ConclusionsOur data showed that NBT-167, a dimer of resveratrol, had anticancer and immunomodulatory activities such as modulation of expression of cytokines in immune cells and induction of cancer cell-killing activities of NK and gamma delta T cells. Generally, NBT-167 appeared to have higher activities than resveratrol in modulating immune cells and inhibiting cancer cells. NBT-167 could be a promising cancer immunotherapeutic agent targeting both cancer cells and immune cells.

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