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CD3+CD4+gp130+ T cells are associated with worse disease activity in systemic Lupus Erythematosus patients


Citation

Mohd Shukri, Nur Diyana and Aziz, Farah Izati and Wan Ghazali, Wan Syamimee and Che Hussin, Che Maraina and Wong, Kah Keng (2021) CD3+CD4+gp130+ T cells are associated with worse disease activity in systemic Lupus Erythematosus patients. Frontiers in Immunology, 12. pp. 1-12. ISSN 1664-3224

Abstract

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.


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Additional Metadata

Item Type: Article
Divisions: Faculty of Medicine and Health Science
DOI Number: https://doi.org/10.3389/fimmu.2021.675250
Publisher: Frontiers Media
Keywords: Systemic lupus erythematosus; Gp130; IL6ST; IL-35; IL-12Rb2; SLEDAI-2K
Depositing User: Ms. Nuraida Ibrahim
Date Deposited: 13 Feb 2023 02:27
Last Modified: 13 Feb 2023 02:27
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.3389/fimmu.2021.675250
URI: http://psasir.upm.edu.my/id/eprint/96308
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