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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| Format: | Article |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.675250/full |
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| author | Nur Diyana Mohd Shukri Nur Diyana Mohd Shukri Aziz Farah Izati Aziz Farah Izati Wan Syamimee Wan Ghazali Wan Syamimee Wan Ghazali Che Maraina Che Hussin Che Maraina Che Hussin Kah Keng Wong Kah Keng Wong |
| author_facet | Nur Diyana Mohd Shukri Nur Diyana Mohd Shukri Aziz Farah Izati Aziz Farah Izati Wan Syamimee Wan Ghazali Wan Syamimee Wan Ghazali Che Maraina Che Hussin Che Maraina Che Hussin Kah Keng Wong Kah Keng Wong |
| author_sort | Nur Diyana Mohd Shukri |
| collection | DOAJ |
| 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 | 2024-12-16T18:21:26Z |
| format | Article |
| id | doaj.art-54af646aa71a4175984b8a904f539baa |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T18:21:26Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-54af646aa71a4175984b8a904f539baa2022-12-21T22:21:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.675250675250CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus PatientsNur Diyana Mohd Shukri0Nur Diyana Mohd Shukri1Aziz Farah Izati2Aziz Farah Izati3Wan Syamimee Wan Ghazali4Wan Syamimee Wan Ghazali5Che Maraina Che Hussin6Che Maraina Che Hussin7Kah Keng Wong8Kah Keng Wong9Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MalaysiaHospital Universiti Sains Malaysia, Kubang Kerian, MalaysiaDepartment of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MalaysiaHospital Universiti Sains Malaysia, Kubang Kerian, MalaysiaHospital Universiti Sains Malaysia, Kubang Kerian, MalaysiaDepartment of Internal Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MalaysiaDepartment of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MalaysiaHospital Universiti Sains Malaysia, Kubang Kerian, MalaysiaDepartment of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MalaysiaHospital Universiti Sains Malaysia, Kubang Kerian, MalaysiaThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.675250/fullsystemic lupus erythematosusgp130IL6STIL-35IL-12Rβ2SLEDAI-2K |
| spellingShingle | Nur Diyana Mohd Shukri Nur Diyana Mohd Shukri Aziz Farah Izati Aziz Farah Izati Wan Syamimee Wan Ghazali Wan Syamimee Wan Ghazali Che Maraina Che Hussin Che Maraina Che Hussin Kah Keng Wong Kah Keng Wong CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients Frontiers in Immunology systemic lupus erythematosus gp130 IL6ST IL-35 IL-12Rβ2 SLEDAI-2K |
| title | 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_short | 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 |
| topic | systemic lupus erythematosus gp130 IL6ST IL-35 IL-12Rβ2 SLEDAI-2K |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.675250/full |
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