CD3CD4gp130 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...
| Main Authors: | , , , , |
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| Format: | Article |
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Frontiers Media
2021
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| Online Access: | http://psasir.upm.edu.my/id/eprint/96307/ |
| _version_ | 1848862332802826240 |
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| author | Mohd Shukri, Nur Diyana Aziz, Farah Izati Wan Ghazali, Wan Syamimee Che Hussin, Che Maraina Kah, Keng Wong |
| author_facet | Mohd Shukri, Nur Diyana Aziz, Farah Izati Wan Ghazali, Wan Syamimee Che Hussin, Che Maraina Kah, Keng Wong |
| author_sort | Mohd Shukri, Nur Diyana |
| building | UPM Institutional Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-15T13:15:21Z |
| format | Article |
| id | upm-96307 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T13:15:21Z |
| publishDate | 2021 |
| publisher | Frontiers Media |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-963072023-01-31T01:58:53Z http://psasir.upm.edu.my/id/eprint/96307/ CD3CD4gp130 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 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. Frontiers Media 2021 Article PeerReviewed Mohd Shukri, Nur Diyana and Aziz, Farah Izati and Wan Ghazali, Wan Syamimee and Che Hussin, Che Maraina and Kah, Keng Wong (2021) CD3CD4gp130 T cells are associated with worse disease activity in systemic lupus erythematosus patients. Frontiers in Immunology, 12. art. no. 675250. pp. 1-12. ISSN 1664-3224 https://www.frontiersin.org/articles/10.3389/fimmu.2021.675250/full 10.3389/fimmu.2021.675250 |
| spellingShingle | Mohd Shukri, Nur Diyana Aziz, Farah Izati Wan Ghazali, Wan Syamimee Che Hussin, Che Maraina Kah, Keng Wong CD3CD4gp130 T cells are associated with worse disease activity in systemic lupus erythematosus patients |
| title | CD3CD4gp130 T cells are associated with worse disease activity in systemic lupus erythematosus patients |
| title_full | CD3CD4gp130 T cells are associated with worse disease activity in systemic lupus erythematosus patients |
| title_fullStr | CD3CD4gp130 T cells are associated with worse disease activity in systemic lupus erythematosus patients |
| title_full_unstemmed | CD3CD4gp130 T cells are associated with worse disease activity in systemic lupus erythematosus patients |
| title_short | CD3CD4gp130 T cells are associated with worse disease activity in systemic lupus erythematosus patients |
| title_sort | cd3cd4gp130 t cells are associated with worse disease activity in systemic lupus erythematosus patients |
| url | http://psasir.upm.edu.my/id/eprint/96307/ http://psasir.upm.edu.my/id/eprint/96307/ http://psasir.upm.edu.my/id/eprint/96307/ |