Impaired Regulation by IL-35 in Systemic Sclerosis
This study investigated the role of IL-35 in systemic sclerosis (SSc) patients, focusing on CD4+ T cell response and immunomodulatory cytokine production. By comparing the cytokine levels in healthy donors (HD) and SSc patients using ELISAs, we found a significantly lower plasma IL-35 concentration...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10567 |
| _version_ | 1797591636079804416 |
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| author | Rubén Osuna-Gómez Ivan Castellví Maria Mulet Mª Àngels Ortiz Douglas E. Brough Helen Sabzevari Roshanak T. Semnani Silvia Vidal |
| author_facet | Rubén Osuna-Gómez Ivan Castellví Maria Mulet Mª Àngels Ortiz Douglas E. Brough Helen Sabzevari Roshanak T. Semnani Silvia Vidal |
| author_sort | Rubén Osuna-Gómez |
| collection | DOAJ |
| description | This study investigated the role of IL-35 in systemic sclerosis (SSc) patients, focusing on CD4+ T cell response and immunomodulatory cytokine production. By comparing the cytokine levels in healthy donors (HD) and SSc patients using ELISAs, we found a significantly lower plasma IL-35 concentration in the SSc patients (52.1 ± 5.6 vs. 143 ± 11.1, <i>p</i> < 0.001). Notably, the IL-35 levels showed a negative correlation with TGF-β (<i>p</i> < 0.001) and IL-17 (<i>p</i> = 0.04). Assessing the IL-35R expression across cell types in the SSc patients and HDs via flow cytometry, we found higher levels on monocytes (40.7 + 5.7 vs. 20.3 ± 1.9, <i>p</i> < 0.001) and lower levels on CD8+ T cells (61.8 ± 9.2 vs. 83.4 ± 0.8, <i>p</i> < 0.05) in the SSc patients. The addition of recombinant IL-35 to stimulated peripheral blood mononuclear cells reduced the IL-17+CD4+ T cell percentage (9.0 ± 1.5 vs. 4.8 ± 0.7, <i>p</i> < 0.05) and increased the IL-35+CD4+ T percentage (4.1 ± 2.3 vs. 10.2 ± 0.8, <i>p</i> < 0.001). In a Treg:Tresponder cell Sco-culture assay with HD and SSc samples, rIL35 decreased the cell proliferation and levels of IL-17A (178.2 ± 30.5 pg/mL vs. 37.4 ± 6.4 pg/mL, <i>p</i> < 0.001) and TGF-β (4194 ± 777 pg/mL vs. 2413 ± 608 pg/mL, <i>p</i> < 0.01). Furthermore, we observed a positive correlation between the modified Rodnan skin score (mRSS) and TGF-β (<i>p</i> < 0.001), while there was a negative correlation between mRSS and IL-35 (<i>p</i> = 0.004). Interestingly, higher levels of plasmatic IL-35 were detected in individuals with limited disease compared to those with diffuse disease (60.1 ± 8.0 vs. 832.3 ± 4.1, <i>p</i> < 0.05). These findings suggest that IL-35 exhibits anti-inflammatory properties in SSc and it may serve as a marker for disease severity and a therapeutic target. |
| first_indexed | 2024-03-11T01:40:07Z |
| format | Article |
| id | doaj.art-774cabab10f841669e7c2c15f77c5d2c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:40:07Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-774cabab10f841669e7c2c15f77c5d2c2023-11-18T16:40:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131056710.3390/ijms241310567Impaired Regulation by IL-35 in Systemic SclerosisRubén Osuna-Gómez0Ivan Castellví1Maria Mulet2Mª Àngels Ortiz3Douglas E. Brough4Helen Sabzevari5Roshanak T. Semnani6Silvia Vidal7Inflammatory Diseases, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainDepartment of Rheumatology and Systemic Autoimmune Diseases, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, SpainInflammatory Diseases, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainInflammatory Diseases, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainPrecigen, Inc., Germantown, MD 20876, USAPrecigen, Inc., Germantown, MD 20876, USAPrecigen, Inc., Germantown, MD 20876, USAInflammatory Diseases, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainThis study investigated the role of IL-35 in systemic sclerosis (SSc) patients, focusing on CD4+ T cell response and immunomodulatory cytokine production. By comparing the cytokine levels in healthy donors (HD) and SSc patients using ELISAs, we found a significantly lower plasma IL-35 concentration in the SSc patients (52.1 ± 5.6 vs. 143 ± 11.1, <i>p</i> < 0.001). Notably, the IL-35 levels showed a negative correlation with TGF-β (<i>p</i> < 0.001) and IL-17 (<i>p</i> = 0.04). Assessing the IL-35R expression across cell types in the SSc patients and HDs via flow cytometry, we found higher levels on monocytes (40.7 + 5.7 vs. 20.3 ± 1.9, <i>p</i> < 0.001) and lower levels on CD8+ T cells (61.8 ± 9.2 vs. 83.4 ± 0.8, <i>p</i> < 0.05) in the SSc patients. The addition of recombinant IL-35 to stimulated peripheral blood mononuclear cells reduced the IL-17+CD4+ T cell percentage (9.0 ± 1.5 vs. 4.8 ± 0.7, <i>p</i> < 0.05) and increased the IL-35+CD4+ T percentage (4.1 ± 2.3 vs. 10.2 ± 0.8, <i>p</i> < 0.001). In a Treg:Tresponder cell Sco-culture assay with HD and SSc samples, rIL35 decreased the cell proliferation and levels of IL-17A (178.2 ± 30.5 pg/mL vs. 37.4 ± 6.4 pg/mL, <i>p</i> < 0.001) and TGF-β (4194 ± 777 pg/mL vs. 2413 ± 608 pg/mL, <i>p</i> < 0.01). Furthermore, we observed a positive correlation between the modified Rodnan skin score (mRSS) and TGF-β (<i>p</i> < 0.001), while there was a negative correlation between mRSS and IL-35 (<i>p</i> = 0.004). Interestingly, higher levels of plasmatic IL-35 were detected in individuals with limited disease compared to those with diffuse disease (60.1 ± 8.0 vs. 832.3 ± 4.1, <i>p</i> < 0.05). These findings suggest that IL-35 exhibits anti-inflammatory properties in SSc and it may serve as a marker for disease severity and a therapeutic target.https://www.mdpi.com/1422-0067/24/13/10567systemic sclerosisinterleukin-35CD4+ T lymphocytesregulatory T cells |
| spellingShingle | Rubén Osuna-Gómez Ivan Castellví Maria Mulet Mª Àngels Ortiz Douglas E. Brough Helen Sabzevari Roshanak T. Semnani Silvia Vidal Impaired Regulation by IL-35 in Systemic Sclerosis International Journal of Molecular Sciences systemic sclerosis interleukin-35 CD4+ T lymphocytes regulatory T cells |
| title | Impaired Regulation by IL-35 in Systemic Sclerosis |
| title_full | Impaired Regulation by IL-35 in Systemic Sclerosis |
| title_fullStr | Impaired Regulation by IL-35 in Systemic Sclerosis |
| title_full_unstemmed | Impaired Regulation by IL-35 in Systemic Sclerosis |
| title_short | Impaired Regulation by IL-35 in Systemic Sclerosis |
| title_sort | impaired regulation by il 35 in systemic sclerosis |
| topic | systemic sclerosis interleukin-35 CD4+ T lymphocytes regulatory T cells |
| url | https://www.mdpi.com/1422-0067/24/13/10567 |
| work_keys_str_mv | AT rubenosunagomez impairedregulationbyil35insystemicsclerosis AT ivancastellvi impairedregulationbyil35insystemicsclerosis AT mariamulet impairedregulationbyil35insystemicsclerosis AT maangelsortiz impairedregulationbyil35insystemicsclerosis AT douglasebrough impairedregulationbyil35insystemicsclerosis AT helensabzevari impairedregulationbyil35insystemicsclerosis AT roshanaktsemnani impairedregulationbyil35insystemicsclerosis AT silviavidal impairedregulationbyil35insystemicsclerosis |