Superoxide Dismutase-1 Intracellular Content in T Lymphocytes Associates with Increased Regulatory T Cell Level in Multiple Sclerosis Subjects Undergoing Immune-Modulating Treatment

Antioxidants

Paolo Mondola¹  Simona Damiano¹  Mariarosaria Santillo¹  Giuliana La Rosa¹  Francesco Aruta²  Rosa Iodice²  Valentina Rubino³  Angela Giovazzino³  Giuseppina Ruggiero³  Flavia Carriero⁴  Giuseppe Terrazzano⁴  Anna Teresa Palatucci⁴ 

[1] Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, Italy;Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, Italy;Dipartimento di Scienze Mediche Traslazionali, Università di Napoli “Federico II”, Via Pansini, 5, 80131 Napoli, Italy;Dipartimento di Scienze, Università della Basilicata, Via dell’Ateneo Lucano, 85100 Potenza, Italy;

关键词: multiple sclerosis;    SOD-1;    T lymphocytes;    Treg;    cytokines;   

DOI  :  10.3390/antiox10121940

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown