Superoxide Dismutase-1 Intracellular Content in T Lymphocytes Associates with Increased Regulatory T Cell Level in Multiple Sclerosis Subjects Undergoing Immune-Modulating Treatment
Reactive oxygen species (ROS) participate in the T-cell activation processes. ROS-dependent regulatory networks are usually mediated by peroxides, which are more stable and able to freely migrate inside cells. Superoxide dismutase (SOD)-1 represents the major physiological intracellular source of pe...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/12/1940 |
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| author | Valentina Rubino Anna Teresa Palatucci Giuliana La Rosa Angela Giovazzino Francesco Aruta Simona Damiano Flavia Carriero Mariarosaria Santillo Rosa Iodice Paolo Mondola Giuseppina Ruggiero Giuseppe Terrazzano |
| author_facet | Valentina Rubino Anna Teresa Palatucci Giuliana La Rosa Angela Giovazzino Francesco Aruta Simona Damiano Flavia Carriero Mariarosaria Santillo Rosa Iodice Paolo Mondola Giuseppina Ruggiero Giuseppe Terrazzano |
| author_sort | Valentina Rubino |
| collection | DOAJ |
| description | Reactive oxygen species (ROS) participate in the T-cell activation processes. ROS-dependent regulatory networks are usually mediated by peroxides, which are more stable and able to freely migrate inside cells. Superoxide dismutase (SOD)-1 represents the major physiological intracellular source of peroxides. We found that antigen-dependent activation represents a triggering element for SOD-1 production and secretion by human T lymphocytes. A deranged T-cell proinflammatory response characterizes the pathogenesis of multiple sclerosis (MS). We previously observed a decreased SOD-1 intracellular content in leukocytes of MS individuals at diagnosis, with increasing amounts of such enzyme after interferon (IFN)-b 1b treatment. Here, we analyzed in depth SOD-1 intracellular content in T cells in a cohort of MS individuals undergoing immune-modulating treatment. Higher amounts of the enzyme were associated with increased availability of regulatory T cells (Treg) preferentially expressing Foxp3-exon 2 (Foxp3-E2), as described for effective Treg. In vitro administration of recombinant human SOD-1 to activated T cells, significantly increased their IL-17 production, while SOD-1 molecules lacking dismutase activity were unable to interfere with cytokine production by activated T cells in vitro. Furthermore, hydrogen peroxide addition was observed to mimic, in vitro, the SOD-1 effect on IL-17 production. These data add SOD-1 to the molecules involved in the molecular pathways contributing to re-shaping the T-cell cytokine profile and Treg differentiation. |
| first_indexed | 2024-03-10T04:38:57Z |
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| id | doaj.art-c98180e09c9b426583aa08eaea886551 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T04:38:57Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-c98180e09c9b426583aa08eaea8865512023-11-23T03:33:13ZengMDPI AGAntioxidants2076-39212021-12-011012194010.3390/antiox10121940Superoxide Dismutase-1 Intracellular Content in T Lymphocytes Associates with Increased Regulatory T Cell Level in Multiple Sclerosis Subjects Undergoing Immune-Modulating TreatmentValentina Rubino0Anna Teresa Palatucci1Giuliana La Rosa2Angela Giovazzino3Francesco Aruta4Simona Damiano5Flavia Carriero6Mariarosaria Santillo7Rosa Iodice8Paolo Mondola9Giuseppina Ruggiero10Giuseppe Terrazzano11Dipartimento di Scienze Mediche Traslazionali, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, ItalyDipartimento di Scienze, Università della Basilicata, Via dell’Ateneo Lucano, 85100 Potenza, ItalyDipartimento di Medicina Clinica e Chirurgia, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, ItalyDipartimento di Scienze Mediche Traslazionali, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, ItalyDipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, ItalyDipartimento di Medicina Clinica e Chirurgia, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, ItalyDipartimento di Scienze, Università della Basilicata, Via dell’Ateneo Lucano, 85100 Potenza, ItalyDipartimento di Medicina Clinica e Chirurgia, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, ItalyDipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, ItalyDipartimento di Medicina Clinica e Chirurgia, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, ItalyDipartimento di Scienze Mediche Traslazionali, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, ItalyDipartimento di Scienze, Università della Basilicata, Via dell’Ateneo Lucano, 85100 Potenza, ItalyReactive oxygen species (ROS) participate in the T-cell activation processes. ROS-dependent regulatory networks are usually mediated by peroxides, which are more stable and able to freely migrate inside cells. Superoxide dismutase (SOD)-1 represents the major physiological intracellular source of peroxides. We found that antigen-dependent activation represents a triggering element for SOD-1 production and secretion by human T lymphocytes. A deranged T-cell proinflammatory response characterizes the pathogenesis of multiple sclerosis (MS). We previously observed a decreased SOD-1 intracellular content in leukocytes of MS individuals at diagnosis, with increasing amounts of such enzyme after interferon (IFN)-b 1b treatment. Here, we analyzed in depth SOD-1 intracellular content in T cells in a cohort of MS individuals undergoing immune-modulating treatment. Higher amounts of the enzyme were associated with increased availability of regulatory T cells (Treg) preferentially expressing Foxp3-exon 2 (Foxp3-E2), as described for effective Treg. In vitro administration of recombinant human SOD-1 to activated T cells, significantly increased their IL-17 production, while SOD-1 molecules lacking dismutase activity were unable to interfere with cytokine production by activated T cells in vitro. Furthermore, hydrogen peroxide addition was observed to mimic, in vitro, the SOD-1 effect on IL-17 production. These data add SOD-1 to the molecules involved in the molecular pathways contributing to re-shaping the T-cell cytokine profile and Treg differentiation.https://www.mdpi.com/2076-3921/10/12/1940multiple sclerosisSOD-1T lymphocytesTregcytokines |
| spellingShingle | Valentina Rubino Anna Teresa Palatucci Giuliana La Rosa Angela Giovazzino Francesco Aruta Simona Damiano Flavia Carriero Mariarosaria Santillo Rosa Iodice Paolo Mondola Giuseppina Ruggiero Giuseppe Terrazzano Superoxide Dismutase-1 Intracellular Content in T Lymphocytes Associates with Increased Regulatory T Cell Level in Multiple Sclerosis Subjects Undergoing Immune-Modulating Treatment Antioxidants multiple sclerosis SOD-1 T lymphocytes Treg cytokines |
| title | Superoxide Dismutase-1 Intracellular Content in T Lymphocytes Associates with Increased Regulatory T Cell Level in Multiple Sclerosis Subjects Undergoing Immune-Modulating Treatment |
| title_full | Superoxide Dismutase-1 Intracellular Content in T Lymphocytes Associates with Increased Regulatory T Cell Level in Multiple Sclerosis Subjects Undergoing Immune-Modulating Treatment |
| title_fullStr | Superoxide Dismutase-1 Intracellular Content in T Lymphocytes Associates with Increased Regulatory T Cell Level in Multiple Sclerosis Subjects Undergoing Immune-Modulating Treatment |
| title_full_unstemmed | Superoxide Dismutase-1 Intracellular Content in T Lymphocytes Associates with Increased Regulatory T Cell Level in Multiple Sclerosis Subjects Undergoing Immune-Modulating Treatment |
| title_short | Superoxide Dismutase-1 Intracellular Content in T Lymphocytes Associates with Increased Regulatory T Cell Level in Multiple Sclerosis Subjects Undergoing Immune-Modulating Treatment |
| title_sort | superoxide dismutase 1 intracellular content in t lymphocytes associates with increased regulatory t cell level in multiple sclerosis subjects undergoing immune modulating treatment |
| topic | multiple sclerosis SOD-1 T lymphocytes Treg cytokines |
| url | https://www.mdpi.com/2076-3921/10/12/1940 |
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