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.

Low Blood Counts of Memory/Effector CD8 T Cells, Gamma/Delta T Cells, Memory B Cells and Plasmacytoid Dendritic Cells and High Counts of Th2 Cells in Systemic Sclerosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4917-4917
Author(s):  
Jan Storek ◽  
Rob Woolson ◽  
Paul K. Wallace ◽  
Gregory Sempowski ◽  
Peter A. McSweeney ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Systemic Sclerosis ◽  
B Cells ◽  
Cd8 T Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Memory B Cells ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Memory Cd8 T Cells

Abstract Abstract 4917 Introduction: Systemic sclerosis (SSc) is presumed to result from aberrant activation of autoreactive T cells. However, the exact pathogenesis of SSc is not known. Patients and Methods: To contribute to the understanding of the immunopathology of systemic sclerosis (SSc), we compared blood counts of multiple lymphocyte subsets between 20 adult SSc patients not treated with immunomodulatory drugs and healthy controls. The patients had to fit entry criteria for SCOT trial (Scleroderma – Cyclophosphamide or Transplantation?, www.sclerodermatrial.org), i.e, 1. symptoms for no longer than 5 years (except for Raynaud's phenomenon), 2. diffuse scleroderma, and 3. either moderate lung involvement (forced vital capacity (FVC) or diffusion of carbon monoxide (DLCO) between 45 and 70% predicted) or moderate kidney involvement (history of hypertensive renal crisis, but normal renal function at study entry). Multiparameter flow cytometry was used for the determination of the lymphocyte subset counts. Results: Counts of the following subsets were significantly lower in the patients compared to the controls: total T cells (median 1316 vs 2088/ul, p=0.015), total CD8 T cells (273 vs 580/ul, p<0.001), central memory CD8 T cells (23 vs 87/ul, p<0.001), effector memory CD8 T cells (17 vs 39/ul, p=0.015), effector CD8 T cells (28 vs 68/ul, p=0.001), gamma/delta T cells (31 vs 77/ul, p<0.001), switched (IgM/DàIgG/A isotype switched) memory B cells (6 vs 26/ul, p<0.001), non-switched memory B cells (7 vs 17/ul, p=0.004), and plasmacytoid dendritic cells (2 vs 6/ul, p=0.002). Counts of Th2-biased (producing interleukin-4 upon polyclonal stimulation) CD4 as well as CD8 T cells were significantly higher in the patients compared to the controls (248 vs 139/ul for CD4, p=0.002, and 259 vs 164/ul for CD8, p<0.001). Conclusion: Immunopathology of SSc is complex. Low blood counts of memory/effector CD8 T cells, gamma/delta T cells, memory B cells and plasmacytoid dendritic cells and Th2-biased T cells may play a role in the pathogenesis of SSc. However, cause and effect relations need to be established. Given previous reports of increased numbers of CD8 and gamma/delta T cells in the affected tissues of patients with systemic sclerosis and increased numbers of plasmacytoid dendritic cells in the affected tissues of patients with autoimmune diseases (compared to healthy individuals) (Prescott RJ et al: J Pathol 166 (1992) 255–63, Atamas SP et al: Arthritis Rheum 42 (1999) 1168–78, Giacomelli R et al: Arthritis Rheum 41 (1998) 327–34, Yurovski VV et al: J Immunol 153 (1994) 881–91, Nestle FO et al: J Exp Med 202 (2005) 35–43, Farkas L et al: Am J Pathol 159 (2001) 237–43), it is possible that the low blood counts of CD8 T cells, gamma/delta T cells and plasmacytoid dendritic cells result from redistribution of these cells from blood to affected tissues. Disclosures: No relevant conflicts of interest to declare.

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

Dendritic Cells Can Be Primed to Concurrently Activate Both Unconventional Gamma/delta and Conventional alpha/beta T Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3893-3893
Author(s):  
Francesca Fiore ◽  
Barbara Castella ◽  
Barbara Nuschak ◽  
Raffaello Bertieri ◽  
Sara Mariani ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Adoptive Cell Therapy ◽  
Effector Memory ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Alpha Beta

Abstract Vgamma9/Vdelta2 (gamma/delta) T cells represent the major subset of unconventional T cells circulating in the peripheral blood. Gamma/delta T cells play a major role in immune defenses against microbes, stressed cells and tumor cells. This property is based on their capability to naturally recognize phosphoantigens (pAgs), which are produced via the mevalonate (Mev) or the DOXP pathway in mammalian and nonmammalian cells, and induced self-ligands, which are de novo expressed or upregulated on the surface of stressed or tumor cells. Interestingly, gamma/delta T cells can also be activated by aminobisphosphonates (ABP)-treated monocytes. We have previously shown that ABP specifically target the Mev pathway of monocytes and induce the accumulation of phosphorylated Mev metabolites naturally recognized by gamma/delta T cells. The aim of this work was to determine whether ABP-treated dendritic cells (DC) can also activate gamma/delta T cells and whether this activation, if any, is detrimental or beneficial to the generation of antigen (Ag)-specific MHC-restricted immune responses mediated by conventional alpha/beta T cells. To this end, we have generated highly purified immature (iDC) and mature DC (mDC) from peripheral blood monocytes of healthy donors and incubated with zoledronic acid (Zol) for 24 hours. Zol is the most potent ABP currently available for clinical use. Zol treatment did not affect the phenotype and immunostimulatory properties of iDC and mDC. Zol-treated iDC and mDC induced a rapid and vigorous expansion of central memory and effector memory gamma/delta T cells. Zol-treated iDC were more potent inducers of gamma/delta T-cell activation than mDC and monocytes. Activated gamma/delta T cells displayed antitumor activity and expressed on the cell surface the appropriate antigen repertoire to target secondary lymphoid organs and exert costimulatory activity on conventional alpha/beta T cells. Indeed, an in vitro model showed that antigen-specific MHC-restricted immune responses againt the influenza matrix peptide were significantly improved by the concurrent activation of gamma/delta T cells. This is the first report showing that: 1) DC can simultaneously be primed to activate both gamma/delta and alpha/beta T cells; 2) the former act as cellular adjuvants for the development of adaptive immune responses. In conclusion, large numbers of gamma/delta T cells with effector and costimulatory activities can rapidly be generated by Zol-treated iDC/mDC. This strategy is worth of further investigation to improve adoptive cell therapy and vaccine interventions against tumors and infections.

Retinal Antigen Specific Lymphocytes, Tcr-Gamma Delta T Cells and Cd5+B Cells Cultured from the Vitreous in Acute Sympathetic Ophthalmitis

Autoimmunity ◽  
1993 ◽  
Vol 15 (4) ◽  
pp. 257-266 ◽  
Author(s):  
Janet Liversidge ◽  
Andrew Dick ◽  
Ying-Feng Cheng ◽  
Geoffrey B. Scott ◽  
John V. Forrester
Keyword(s):  
T Cells ◽  
B Cells ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Sympathetic Ophthalmitis ◽  
Retinal Antigen ◽  
Cells Cultured

scholarly journals Interleukin (IL)-4 inhibits IL-10 to promote IL-12 production by dendritic cells

2005 ◽  
Vol 201 (12) ◽  
pp. 1899-1903 ◽  
Author(s):  
Yongxue Yao ◽  
Wei Li ◽  
Mark H. Kaplan ◽  
Cheong-Hee Chang
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Dendritic Cells ◽  
Cell Differentiation ◽  
B Cells ◽  
Histone Acetylation ◽  
Cell Lineage ◽  
Down Regulation ◽  
Th1 Cell ◽  
Th2 Cell

Interleukin (IL)-4 is known to be the most potent cytokine that can initiate Th2 cell differentiation. Paradoxically, IL-4 instructs dendritic cells (DCs) to promote Th1 cell differentiation. We investigated the mechanisms by which IL-4 directs CD4 T cells toward the Th1 cell lineage. Our study demonstrates that the IL-4–mediated induction of Th1 cell differentiation requires IL-10 production by DCs. IL-4 treatment of DCs in the presence of lipopolysaccharide or CpG resulted in decreased production of IL-10, which was accompanied by enhanced IL-12 production. In IL-10–deficient DCs, the level of IL-12 was greatly elevated and, more importantly, the ability of IL-4 to up-regulate IL-12 was abrogated. Interestingly, IL-4 inhibited IL-10 production by DCs but not by B cells. The down-regulation of IL-10 gene expression by IL-4 depended on Stat6 and was at least partly caused by decreased histone acetylation of the IL-10 promoter. These data indicate that IL-4 plays a key role in inducing Th1 cell differentiation by instructing DCs to produce less IL-10.

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.

Gene expression profile in human leukocytes

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3509-3513 ◽  
Author(s):  
Shin-ichi Hashimoto ◽  
Shigenori Nagai ◽  
Jun Sese ◽  
Takuji Suzuki ◽  
Aya Obata ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Memory T Cells ◽  
Expression Profiles ◽  
Molecular Signature ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Human Leukocytes

Leukocytes are classified as myelocytic or lymphocytic, and each class of leukocytes consists of several types of cells that have different phenotypes and different roles. To define the gene expression in these cells, we have performed serial analysis of gene expression (SAGE) using human leukocytes and have provided the gene database for these cells not only at the resting stage but also at the activated stage. A total of 709 990 tags from 17 libraries were analyzed for the manifestation of gene expression profiles in various types of human leukocytes. Types of leukocytes analyzed were as follows: peripheral blood monocytes, colony-stimulating factor–induced macrophages, monocyte-derived immature dendritic cells, mature/activated dendritic cells, granulocytes, natural killer (NK) cells, resting B cells, activated B cells, naive T cells, CCR4− memory T cells (resting TH1 cells), CCR4+ memory T cells (resting TH2 cells), activated TH1 cells, and activated TH2 cells. Among 38 961 distinct tags that appeared more than once in the combined total libraries, 27 323 tags were found to represent unique genes in certain type(s) of leukocytes. Using probability (P) and hierarchical clustering analysis, we identified the genes selectively expressed in each type of leukocytes. Identification of the genes specifically expressed in different types of leukocytes provides not only a novel molecular signature to define different subsets of resting and activated cells but also contributes to further understanding of the biologic function of leukocytes in the host defense system.

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 γ/δ T lymphocytes express CD40 ligand and induce isotype switching in B lymphocytes.

1995 ◽  
Vol 181 (3) ◽  
pp. 1239-1244 ◽  
Author(s):  
A A Horner ◽  
H Jabara ◽  
N Ramesh ◽  
R S Geha
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
B Cells ◽  
Cd40 Ligand ◽  
Surface Expression ◽  
Epithelial Tissue ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Isotype Switching ◽  
Ige Synthesis

T cells expressing gamma/delta T cell receptors home to epithelial tissue and may play a role in immunity to infectious agents and foreign antigens. In an effort to understand the role of gamma/delta T cells in directing B cell responses, we investigated the capacity of human gamma/delta T cells to express CD40 ligand (CD40L) and to drive immunoglobulin (Ig) isotype switching in B cells. A multiple step purification procedure resulted in the recovery of highly pure populations of peripheral blood CD4-CD8- gamma/delta T cells. Neither CD40L surface expression nor CD40L mRNA were detected in unstimulated gamma/delta T cells. Stimulation with phorbol ester and ionomycin induced CD40L mRNA and surface CD40L expression by gamma/delta T cells. Both the percentage of CD40L+ cells and the cell surface density of CD40L were significantly lower in gamma/delta T cells compared to unselected T cells. We further demonstrated that in the presence of neutralizing monoclonal antibody to interferon gamma (IFN-gamma), gamma/delta T cells could induce IgE synthesis in B cells, albeit to a lesser extent than unselected T cells. Furthermore, IgE synthesis driven by gamma/delta T cells was inhibited by monoclonal antibody to CD40L. These observations demonstrate that activated gamma/delta T cells express CD40L and can induce isotype switching in B cells.

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