Impaired Regulation by IL-35 in Systemic Sclerosis
Osuna Gómez, Rubén (Institut d'Investigació Biomèdica Sant Pau)
Castellvi, Ivan (Institut d'Investigació Biomèdica Sant Pau)
Mulet Gual, Maria (Institut d'Investigació Biomèdica Sant Pau)
Ortiz, M. Àngels (Institut d'Investigació Biomèdica Sant Pau)
Brough, Douglas E. (Precigen. Inc)
Sabzevari, Helen (Precigen. Inc)
Semnani, Roshanak T. (Precigen. Inc)
Vidal, Silvia (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	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, p < 0. 001). Notably, the IL-35 levels showed a negative correlation with TGF-β (p < 0. 001) and IL-17 (p = 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, p < 0. 001) and lower levels on CD8+ T cells (61. 8 ± 9. 2 vs. 83. 4 ± 0. 8, p < 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, p < 0. 05) and increased the IL-35+CD4+ T percentage (4. 1 ± 2. 3 vs. 10. 2 ± 0. 8, p < 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, p < 0. 001) and TGF-β (4194 ± 777 pg/mL vs. 2413 ± 608 pg/mL, p < 0. 01). Furthermore, we observed a positive correlation between the modified Rodnan skin score (mRSS) and TGF-β (p < 0. 001), while there was a negative correlation between mRSS and IL-35 (p = 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, p < 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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	CD4+ T lymphocytes ; Interleukin-35 ; Regulatory T cells ; Systemic sclerosis
Published in:	International journal of molecular sciences, Vol. 24 Núm. 13 (july 2023) , p. 10567, ISSN 1422-0067

DOI: 10.3390/ijms241310567
PMID: 37445745

14 p, 2.8 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles