Aberrant GITR expression on different T cell subsets and the regulation by glucocorticoid in systemic lupus erythematosus

2014 ◽  
Vol 19 (2) ◽  
pp. 199-204 ◽  
Author(s):  
Jiafeng Sun ◽  
Ning Yu ◽  
Xiangpei Li ◽  
Li Wang ◽  
Yun Pan ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Nur Diyana Mohd Shukri ◽  
Aziz Farah Izati ◽  
Wan Syamimee Wan Ghazali ◽  
Che Maraina Che Hussin ◽  
Kah Keng Wong

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.


1979 ◽  
Vol 64 (5) ◽  
pp. 1213-1220 ◽  
Author(s):  
Kunio Okudaira ◽  
Hidenori Nakai ◽  
Tetsuo Hayakawa ◽  
Takamichi Kashiwado ◽  
Kiyoaki Tanimoto ◽  
...  

1987 ◽  
Vol 79 (3) ◽  
pp. 762-768 ◽  
Author(s):  
C Morimoto ◽  
A D Steinberg ◽  
N L Letvin ◽  
M Hagan ◽  
T Takeuchi ◽  
...  

Lupus ◽  
2019 ◽  
Vol 28 (10) ◽  
pp. 1214-1223
Author(s):  
S Minning ◽  
Y Xiaofan ◽  
X Anqi ◽  
G Bingjie ◽  
S Dinglei ◽  
...  

Objective The aim of this study was to evaluate the changes in CD8+CD28–/CD8+CD28+ T-cell subset balance and in the CD8+CD28– Treg cell number and function in patients with systemic lupus erythematosus (SLE). Methods Cell isolation and flow cytometry analysis were employed to investigate the T-cell subsets. Results It was found that in high-activity SLE patients, the CD8+CD28+ T-cell subset was reduced, which was inversely correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and that the CD8+CD28–/CD8+CD28+ ratio was elevated, which was positively correlated with SLEDAI and with renal damage and inversely correlated with serum complement level, whereas the CD8+CD28– T-cell subset was increased only in inactive patients. It was also found that apoptosis of CD8+ T cells increased, and Fas, Fas ligand (FasL) and interleukin (IL)-6 expression were high, whereas cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) expression was low by the CD8+CD28+ T cell subset in active SLE patients; apoptosis was positively correlated with SLEDAI and with the expression of Fas and FasL by the CD8+CD28+ T-cell subset in active SLE patients. IL-6 and CTLA-4 expression were found to be low by the CD8+CD28– T cell subset in active SLE patients. Conclusion These data suggest that high expression of Fas, FasL and IL-6 and low expression of CTLA-4 by the CD8+CD28+ T-cell subset promotes the activation-induced cell death of the CD8+CD28+ T-cell subset, resulting in an imbalance of CD8+CD28–/CD8+CD28+ T cells in active SLE patients, which represents an important feature in the immunological pathogenesis of SLE. The CD8+CD28– T-cell subset may play some role in inactive SLE.


2016 ◽  
Vol 22 (9) ◽  
pp. 991-993 ◽  
Author(s):  
Jing He ◽  
Xia Zhang ◽  
Yunbo Wei ◽  
Xiaolin Sun ◽  
Yaping Chen ◽  
...  

2014 ◽  
Vol 33 (8) ◽  
pp. 1085-1091 ◽  
Author(s):  
Azza A. Eltayeb ◽  
Douaa M. Sayed ◽  
Noha A. Afifi ◽  
Maggie A. Ibrahim ◽  
Tahra M. Sheref

2010 ◽  
Vol 37 (8) ◽  
pp. 1658-1666 ◽  
Author(s):  
LANG-JING ZHU ◽  
CAROLINA LANDOLT-MARTICORENA ◽  
TIMOTHY LI ◽  
XIAO YANG ◽  
XUE-QING YU ◽  
...  

Objective.To investigate the expression of tumor necrosis factor receptors (TNFR1 and TNFR2) and adapter proteins (TRADD, RIP, and TRAF2) in peripheral blood mononuclear cell (PBMC) subsets from patients with systemic lupus erythematosus (SLE).Methods.PBMC were isolated from 45 SLE patients and 25 controls, and stained with labeled antibodies that enabled identification of various T cell, B cell, and monocyte subpopulations. Expression of TNF-related signaling molecules was measured by staining with labeled antibodies either directly or following fixation and permeabilization. Apoptosis was quantified using an anti-active caspase 3 antibody. RNA expression of TNF-related signaling molecules was assessed by quantitative RT-PCR and serum levels of TNF-α by ELISA.Results.SLE patients had increased levels of TNFR1, TNFR2, and TRAF2, together with decreased levels of RIP, on various B, CD4+ T, and CD8+ T cell subsets as compared to controls. This altered expression was seen in both naive and memory subpopulations, and reflected altered staining of the whole population rather than a subset of cells that were activated. The levels of these molecules were not significantly correlated with serum TNF-α levels or their RNA expression in whole peripheral blood. TNFR1 and TNFR2 expression was negatively correlated with disease activity. There was no association between the proportion of apoptotic cells in any of the subpopulations and serum TNF-α levels or expression of TNF-related signaling molecules.Conclusion.Patients with SLE had altered expression of TNF-related signaling molecules, suggesting that there may be an imbalance in TNF-α signaling favoring cellular activation as opposed to proapoptotic pathways.


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