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

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

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 s...

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Main Authors:	Mohd Shukri, Nur Diyana, Aziz, Farah Izati, Wan Ghazali, Wan Syamimee, Che Hussin, Che Maraina, Wong, Kah Keng
Format:	Article
Published:	Frontiers Media 2021
Online Access:	http://psasir.upm.edu.my/id/eprint/96308/ https://www.frontiersin.org/articles/10.3389/fimmu.2021.675250/full
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spelling	my.upm.eprints.963082023-02-13T02:27:05Z http://psasir.upm.edu.my/id/eprint/96308/ CD3+CD4+gp130+ T cells are associated with worse disease activity in systemic Lupus Erythematosus patients Mohd Shukri, Nur Diyana Aziz, Farah Izati Wan Ghazali, Wan Syamimee Che Hussin, Che Maraina Wong, Kah Keng 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. Frontiers Media 2021 Article PeerReviewed 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 https://www.frontiersin.org/articles/10.3389/fimmu.2021.675250/full 10.3389/fimmu.2021.675250
institution	Universiti Putra Malaysia
building	UPM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Putra Malaysia
content_source	UPM Institutional Repository
url_provider	http://psasir.upm.edu.my/
description	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.
format	Article
author	Mohd Shukri, Nur Diyana Aziz, Farah Izati Wan Ghazali, Wan Syamimee Che Hussin, Che Maraina Wong, Kah Keng
spellingShingle	Mohd Shukri, Nur Diyana Aziz, Farah Izati Wan Ghazali, Wan Syamimee Che Hussin, Che Maraina Wong, Kah Keng CD3+CD4+gp130+ T cells are associated with worse disease activity in systemic Lupus Erythematosus patients
author_facet	Mohd Shukri, Nur Diyana Aziz, Farah Izati Wan Ghazali, Wan Syamimee Che Hussin, Che Maraina Wong, Kah Keng
author_sort	Mohd Shukri, Nur Diyana
title	CD3+CD4+gp130+ T cells are associated with worse disease activity in systemic Lupus Erythematosus patients
title_short	CD3+CD4+gp130+ T cells are associated with worse disease activity in systemic Lupus Erythematosus patients
title_full	CD3+CD4+gp130+ T cells are associated with worse disease activity in systemic Lupus Erythematosus patients
title_fullStr	CD3+CD4+gp130+ T cells are associated with worse disease activity in systemic Lupus Erythematosus patients
title_full_unstemmed	CD3+CD4+gp130+ T cells are associated with worse disease activity in systemic Lupus Erythematosus patients
title_sort	cd3+cd4+gp130+ t cells are associated with worse disease activity in systemic lupus erythematosus patients
publisher	Frontiers Media
publishDate	2021
url	http://psasir.upm.edu.my/id/eprint/96308/ https://www.frontiersin.org/articles/10.3389/fimmu.2021.675250/full
_version_	1758579860152778752
score	13.211869

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

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