scholarly journals Elevated Apoptosis and Impaired Proliferation Contribute to Downregulated PeripheralγδT Cells in Patients with Systemic Lupus Erythematosus

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Zhimin Lu ◽  
Dinglei Su ◽  
Dandan Wang ◽  
Xia Li ◽  
Xuebing Feng ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Healthy Controls ◽  
Intracellular Cytokine ◽  
Systemic Lupus ◽  
Proliferation Ability

Objective. To investigate the frequency of peripheralγδT cells in patients with systemic lupus erythematosus (SLE) and its correlation with disease activity and to analyze the apoptotic status, proliferation ability, and intracellular cytokine profile of these cells.Methods. Flow cytometry was performed to detect the percentage and intracellular cytokine expression of peripheralγδT cells from SLE patients. Annexin-V/PI double staining was applied to determine the proportion of apoptoticγδand CD3+T cells.γδT cell proliferation was analyzed by CFSE labeling technique.Results. The percentage and absolute number ofγδT cells were remarkably decreased in active SLE patients compared to those in inactive patients and healthy controls, withγδT cell count negatively correlated with disease activity. Compared with healthy controls, peripheralγδT cells from active SLE patients exhibited higher apoptotic rate and lower proliferation ability, as well as elevated expression of intracellular IFN-γ, IL-4, IL-10, and TGF-β, but not IL-17 or Foxp3.Conclusion. DecreasedγδT cells in the peripheral blood of SLE patients might be caused by upregulated apoptosis and downregulated cell proliferation. TheseγδT cells may secret both pro- and anti-inflammatory cytokines to perform their functions in SLE.

scholarly journals CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Nur Diyana Mohd Shukri ◽  
Aziz Farah Izati ◽  
Wan Syamimee Wan Ghazali ◽  
Che Maraina Che Hussin ◽  
Kah Keng Wong
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Lymphocyte Subpopulations ◽  
Gene Set Enrichment Analysis ◽  
T Cell Subsets ◽  
Healthy Controls ◽  
Systemic Lupus

The receptors for IL-35, IL-12Rβ2 and gp130, have been implicated in the inflammatory pathophysiology of autoimmune diseases. In this study, we set out to investigate the serum IL-35 levels and the surface levels of IL-12Rβ2 and gp130 in CD3+CD4+, CD3+CD4─ and CD3─CD4─ lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients (n=50) versus healthy controls (n=50). The potential T cell subsets associated with gp130 transcript (i.e. IL6ST) expression in CD4+ T cells of SLE patients was also examined in publicly-available gene expression profiling (GEP) datasets. Here, we report that serum IL-35 levels were significantly higher in SLE patients than healthy controls (p=0.038) but it was not associated with SLEDAI-2K scores. The proportions of IL-12Rβ2+ and gp130+ cells in SLE patients did not differ significantly with those of healthy controls in all lymphocyte subpopulations investigated. Essentially, higher SLEDAI-2K scores were positively correlated with increased proportion of gp130+ cells, but not IL-12Rβ2+ cells, on CD3+CD4+ T cells (r=0.425, p=0.002, q=0.016). Gene Set Enrichment Analysis (GSEA) of a GEP dataset of CD4+ T cells isolated from SLE patients (n=8; GSE4588) showed that IL6ST expression was positively associated with genes upregulated in CD4+ T cells vs myeloid or B cells (q<0.001). In an independent GEP dataset of CD4+ T cells isolated from SLE patients (n=9; GSE1057), IL6ST expression was induced upon anti-CD3 stimulation, and that Treg, TCM and CCR7+ T cells gene sets were significantly enriched (q<0.05) by genes highly correlated with IL6ST expression (n=92 genes; r>0.75 with IL6ST expression) upon anti-CD3 stimulation in these SLE patients. In conclusion, gp130 signaling in CD3+CD4+ T cell subsets may contribute to increased disease activity in SLE patients, and it represents a promising therapeutic target for inhibition in the disease.

scholarly journals Tim-3 associated with apoptotic NK cells and disease activity in SLE

2021 ◽  
Vol 19 ◽  
pp. 205873922110005
Author(s):  
Di Zhao ◽  
Xiao Yang ◽  
Jie Zhang ◽  
Yi Zhang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Flow Cytometry ◽  
T Cell ◽  
Disease Activity ◽  
Nk Cells ◽  
Lupus Erythematosus ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Potential Target

T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) has been found to play important roles in systemic lupus erythematosus (SLE), however, whether Tim-3 is involved in apoptosis of NK cells in SLE remains unknown. The proportion of CD3−CD56+ NK cells and the percentage of AnnexinV+ NK cells were analyzed by flow cytometry in SLE patients and healthy controls. Tim-3 expression on NK cells was also evaluated by flow cytometry. We firstly observed a decreased proportion of NK cells and an increased proportion of apoptotic NK cells in SLE patients. The proportion of apoptotic NK cells was positively correlated with anti-dsDNA and SLEDAI. Tim-3 expression on NK cells was up-regulated in SLE patients. Further analysis showed that Tim-3 expression on NK cells was negatively correlated with the proportion of apoptotic NK cells, anti-dsDNA and SLEDAI, while positively correlated with the proportion of NK cells. The present results suggest that Tim-3 might play roles in SLE by regulating the apoptosis of NK cells and Tim-3 might serve as a potential target for the treatment of SLE.

scholarly journals Dysregulated T Cell Activation and Aberrant Cytokine Expression Profile in Systemic Lupus Erythematosus

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Haiyan Zhou ◽  
Bojiang Li ◽  
Jing Li ◽  
Tongqian Wu ◽  
Xiaoqian Jin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Critical Role ◽  
Cytokine Expression ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Hla Dr ◽  
Dsdna Antibody

Accumulating evidence indicates a critical role for T cells and relevant cytokines in the pathogenesis of systemic lupus erythematosus (SLE). However, the specific contribution of T cells together with the related circulating cytokines in disease pathogenesis and organ involvement is still not clear. In the current study, we investigated relevant molecule expressions and cytokine levels in blood samples from 49 SLE patients and 22 healthy control subjects. The expression of HLA-DR and costimulatory molecules on T cells was evaluated by flow cytometry. Concentrations of serum C-reactive protein, erythrocyte sedimentation rate, anti-double-stranded DNA (anti-dsDNA) antibody, total lgG, complement 3, and complement 4 were measured. Serum cytokines and chemokines were measured by a cytometric bead array assay. Elevated frequencies of HLA-DR+ T cells and ICOS+ T cells were observed in SLE patients with positive anti-dsDNA antibodies compared with those in healthy controls (P<0.001). The expression of HLA-DR+ T cells was positively correlated with SLEDAI (r=0.15, P<0.01). Furthermore, levels of serum IL-6, MCP-1, TNFRI, IL-10, IL-12, and CCL20 were higher in SLE patients compared with healthy controls. In addition, patients with hematologic manifestations displayed elevated frequencies of HLA-DR+ T cells and ICOS+ T cells. Patients with renal manifestations had a decreased frequency of TIGIT+ T cells. These results suggested a dysregulated T cell activity and cytokine expression profiles in SLE subjects. We also developed a chemokine and cytokine profiling strategy to predict the activity of SLE, which has clinical implication for better monitoring the flares and remission during the course of SLE and for assessing therapeutic interventions.

Associations of site-specific CD4+-T-cell hypomethylation within CD40-ligand promotor and enhancer regions with disease activity of women with systemic lupus erythematosus

Lupus ◽  
2020 ◽  
Vol 30 (1) ◽  
pp. 45-51
Author(s):  
Stefan Vordenbäumen ◽  
Anna Rosenbaum ◽  
Claudia Gebhard ◽  
Johanna Raithel ◽  
Alexander Sokolowski ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Cd40 Ligand ◽  
Systemic Lupus ◽  
Site Specific

Objective To comprehensively assess associations of site-specific CD4+-T-cell hypomethylation of the CD40-Ligand gene ( CD40L) with disease activity of women with systemic lupus erythematosus (SLE). Methods CpG-sites within the DNA of the promotor and two enhancer regions (n = 22) of CD40L were identified and numbered consecutively. The rate of methylated DNA in isolated CD4+-T-cells of women with SLE were quantified for each methylation site by MALDI-TOF. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Associations of site-specific methylation rates with the SLEDAI scores were assessed by linear regression modelling. P values were adjusted according to Bonferroni-Holm as indicated. Results 60 female SLE patients participated in the study (age 45.7 ± 11.1 years, disease duration 17.0 ± 8.3 years). Significant associations to the SLEDAI were noted for CpG22 hypomethylation of the promotor (β = −40.1, p = 0.017, adjusted p = 0.027), trends were noted for CpG17 hypomethylation of the promotor (β = −30.5, p = 0.032, adjusted p = 0.6), and for CpG11 hypermethylation of the second enhancer (β = 15.0, p = 0.046, adjusted p = 0.8). Conclusion Site-specific hypomethylation of the CD40L promotor in CD4+-T-cells show associations with disease activity in female SLE patients.

scholarly journals Relationship between T lymphocyte subsets and cortisol in systemic lupus erythematosus

1970 ◽  
Vol 7 (3) ◽  
pp. 213-219 ◽  
Author(s):  
D Shah ◽  
R Kiran ◽  
A Wanchu ◽  
A Bhatnagar
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Lupus Erythematosus ◽  
Serum Cortisol ◽  
Cd8 T Cell ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
T Lymphocyte Subsets

Background: Systemic Lupus Erythematosus (SLE) is a complex chronic immunological disease characterized by increased B cell activity and altered T cell function. Objective: To investigate relationship between T lymphocyte subsets and cortisol with the disease activity of systemic lupus erythematosus patients in North India. Materials and methods: The percentage of CD4+ and CD8+ T cells in the lymphocyte of SLE patients and healthy controls were determined by flow cytometry. Serum cortisol of SLE patients and healthy controls was determined by enzyme-linked immunosorbent assay (ELISA). Results: A significant decrease in the percentage of CD4+ T cells and increase in the percentage of CD8+ T cells were found in patients with SLE compared to the healthy controls. Decrease in the ratio of CD4+/CD8+ T cell and low level of serum cortisol were found in the patients with SLE. The ratio of CD4+/CD8+ T cell was inversely correlated with systemic lupus erythematosus disease activity index (SLEDAI) score and erythrocyte sedimentation rate (ESR). A positive correlation was observed between CD8+ T cells and SLEDAI score. Furthermore, CD8+ T cells were positively correlated with ESR in the patients with SLE. Conclusion: The results showed that low level of cortisol and high percentage of CD8+ T cells in the lymphocytes could be actively involved in the pathogenesis of SLE. Key words: CD4+/CD8+ T cell ratio; cortisol; systemic lupus erythematosus; T-cell activation DOI: 10.3126/kumj.v7i3.2726 Kathmandu University Medical Journal (2009) Vol.7, No.3 Issue 27, 213-219

scholarly journals Low-density granulocytes activate T cells and demonstrate a non-suppressive role in systemic lupus erythematosus

2019 ◽  
Vol 78 (7) ◽  
pp. 957-966 ◽  
Author(s):  
Saifur Rahman ◽  
Divya Sagar ◽  
Richard N Hanna ◽  
Yaima L Lightfoot ◽  
Pragnesh Mistry ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cytokine Production ◽  
Low Density ◽  
Dependent Manner ◽  
Systemic Lupus ◽  
Lymphocyte Ratio

ObjectivesThe presence of proinflammatory low-density granulocytes (LDG) has been demonstrated in autoimmune and infectious diseases. Recently, regulatory neutrophilic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) were identified in systemic lupus erythematosus (SLE). Because LDG and PMN-MDSC share a similar phenotype with contrasting functional effects, we explored these cells in a cohort of patients with SLE.MethodsLDG and normal-density granulocytes (NDG) were isolated from fresh blood of healthy donors (HD) and patients with SLE. Associations between LDG and clinical manifestations were analysed. Multicolor flow cytometry and confocal imaging were performed to immunophenotype the cells. The ability of LDG and NDG to suppress T cell function and induce cytokine production was quantified.ResultsLDG prevalence was elevated in SLE versus HD, associated with the interferon (IFN) 21-gene signature and disease activity. Also, the LDG-to-lymphocyte ratio associated better with SLE disease activity index than neutrophil-to-lymphocyte ratio. SLE LDG exhibited significantly heightened surface expression of various activation markers and also of lectin-like oxidised low-density lipoprotein receptor-1, previously described to be associated with PMN-MDSC. Supernatants from SLE LDG did not restrict HD CD4+ T cell proliferation in an arginase-dependent manner, suggesting LDG are not immunosuppressive. SLE LDG supernatants induced proinflammatory cytokine production (IFN gamma, tumour necrosis factor alpha and lymphotoxin alpha) from CD4+ T cells.ConclusionsBased on our results, SLE LDG display an activated phenotype, exert proinflammatory effects on T cells and do not exhibit MDSC function. These results support the concept that LDG represent a distinct proinflammatory subset in SLE with pathogenic potential, at least in part, through their ability to activate type 1 helper responses.

Effector T-cells are expanded in systemic lupus erythematosus patients with high disease activity and damage indexes

Lupus ◽  
2017 ◽  
Vol 27 (1) ◽  
pp. 143-149 ◽  
Author(s):  
S Piantoni ◽  
F Regola ◽  
A Zanola ◽  
L Andreoli ◽  
F Dall’Ara ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Damage Index ◽  
Effector T Cells ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
Healthy Controls ◽  
Systemic Lupus

Background and objectives T-cell activation may be one of the pathogenic mechanisms of systemic lupus erythematosus (SLE). After repeated antigenic stimulation, T-cells undergo different modifications, leading to the differentiation into effector memory T-cells (CCR7−CD45RA−) and terminally differentiated effector memory (TDEM) T-cells (CCR7−CD45RA+). Similarly, down-modulation of CD28 may lead to the expansion of the CD28− T-cells, a subpopulation with peculiar effector activities. The aim of this study was the characterization of T-cell phenotype in a cohort of patients with SLE according to disease activity and damage index. Materials and methods Phenotypic analysis of peripheral blood T lymphocytes of 51 SLE patients and 21 healthy controls was done by flow-cytometry. SLE disease activity was evaluated by SLE Disease Activity Index-2000 (SLEDAI-2K) and damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). The variations between different groups were evaluated by Mann–Whitney test. Bonferroni correction was applied to adjust for multiple comparisons ( padj). Spearman rank test was used to evaluate the correlations between quantitative variables. Results CD4+ lymphopenia was found among SLE patients. Patients showed a trend for a higher percentage of TDEM among the CD4+ T-cell subpopulation in comparison with healthy controls ( p = .04). SLE patients were divided into two groups according to disease activity: patients with SLEDAI-2K ≥ 6 ( n = 13) had a higher percentage of circulating CD4+ T-cells with CD28− phenotype ( padj = .005) as well as those with an effector memory ( padj = .004) and TDEM ( padj = .002) phenotype and a trend of decrease of regulatory T-cells (TREGs) ( p = .02), in comparison with patients with low disease activity ( n = 38). Patients with damage (SDI ≥ 1) tended to show an expansion of TDEM among CD4+ T-cells as compared with patients with no damage ( p = .01). In SLE patients an inverse correlation was found between the percentages of TREGs and those of TDEM ( p < .01) or CD4 + CD28− ( p < .01) T-cells. Conclusions CD4+ T-cell subpopulations displaying phenotype characteristics of effector lymphocytes are proportionally expanded in patients with active SLE and a higher damage index. These findings may suggest a role of effector T-cells in the pathogenesis of the disease and in the mechanisms of damage in SLE.

scholarly journals A Novel Long Noncoding RNA lincRNA00892 Activates CD4+ T Cells in Systemic Lupus Erythematosus by Regulating CD40L

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao Liu ◽  
Jinran Lin ◽  
Hao Wu ◽  
Yilun Wang ◽  
Lin Xie ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Hnrnp K ◽  
Qrt Pcr ◽  
Potential Target

Objective: The mechanism of CD4+ T-cell dysfunction in systemic lupus erythematosus (SLE) has not been fully understood. Increasing evidence show that long noncoding RNAs (lncRNAs) can regulate immune responses and take part in some autoimmune diseases, while little is known about the lncRNA expression and function in CD4+ T of SLE. Here, we aimed to detect the expression profile of lncRNAs in lupus CD4+ T cells and explore the mechanism that how lincRNA00892 in CD4+ T cells is involved in the pathogenesis of SLE.Methods: The expression profiles of lncRNAs and mRNAs in CD4+ T cells from SLE patients and healthy controls were detected by microarray. LincRNA00892 and CD40L were chosen for validation by quantitative real-time PCR (qRT-PCR). Coexpression network was conducted to predict the potential target genes of lincRNA00892. Then lincRNA00892 was overexpressed in normal CD4+ T cells via lentivirus transfection. The expression of lincRNA00892 was detected by qRT-PCR. The expression of CD40L was detected by qRT-PCR, western blotting, and flow cytometry, respectively. The expression of CD69 and CD23 was measured by flow cytometry. The secretion of IgG was determined by enzyme-linked immunosorbent assay (ELISA). The proteins targeted by lincRNA00892 were measured by RNA pulldown and subsequent mass spectrometry (MS). The interaction between heterogeneous nuclear ribonucleoprotein K (hnRNP K) and lincRNA00892 or CD40L was detected by RNA immunoprecipitation (RIP) assay.Results: A total of 1887 lncRNAs and 3375 mRNAs were found to be aberrantly expressed in CD4+ T cells of SLE patients compared to healthy controls. LincRNA00892 and CD40L were confirmed to be upregulated in CD4+ T cells of SLE patients by qRT-PCR. The lncRNA–mRNA coexpression network analysis indicated that CD40L was a potential target of lincRNA00892. Overexpression of lincRNA00892 enhanced CD40L protein levels while exerting little influence on CD40L mRNA levels in CD4+ T cells. In addition, lincRNA00892 could induce the activation of CD4+ T cells. Furthermore, lincRNA00892 led to the activation of B cells and subsequent secretion of IgG in a CD4+ T-cell–dependent manner. Finally, hnRNP K was found to be among the proteins pulled down by lincRNA00892, and hnRNP K could bind to lincRNA00892 or CD40L directly.Conclusion: Our results showed that the lncRNA expression profile was altered in CD4+ T cells of SLE. LincRNA00892 possibly contributed to the pathogenesis of SLE by targeting hnRNP K and subsequently upregulating CD40L expression to activate CD4+ T and B cells. These provided us a potential target for further mechanistic studies of SLE pathogenesis.

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