Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients

The altered numbers and functions of cells belonging to immunoregulatory cell networks such as T regulatory (Tregs) and invariant Natural Killer T (iNKT) cells have been reported in Multiple Sclerosis (MS), an immune-mediated disease. We aimed to assess the frequencies of Tregs and iNKT cells in MS...

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Main Authors: Diana Ferraro, Sara De Biasi, Anna Maria Simone, Riccardo Orlandi, Milena Nasi, Francesca Vitetta, Marcello Pinti, Marco Fogliani, Stefano Meletti, Andrea Cossarizza, Patrizia Sola
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/12/3324
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author Diana Ferraro
Sara De Biasi
Anna Maria Simone
Riccardo Orlandi
Milena Nasi
Francesca Vitetta
Marcello Pinti
Marco Fogliani
Stefano Meletti
Andrea Cossarizza
Patrizia Sola
author_facet Diana Ferraro
Sara De Biasi
Anna Maria Simone
Riccardo Orlandi
Milena Nasi
Francesca Vitetta
Marcello Pinti
Marco Fogliani
Stefano Meletti
Andrea Cossarizza
Patrizia Sola
author_sort Diana Ferraro
collection DOAJ
description The altered numbers and functions of cells belonging to immunoregulatory cell networks such as T regulatory (Tregs) and invariant Natural Killer T (iNKT) cells have been reported in Multiple Sclerosis (MS), an immune-mediated disease. We aimed to assess the frequencies of Tregs and iNKT cells in MS patients throughout a one-year treatment with fingolimod (FTY) and to correlate immunological data with efficacy and safety data. The percentage of Tregs (defined as Live Dead-CD3 + CD4 + FoxP3 + CD25++/CD127− cells) increased steadily throughout the year, while there was no significant difference in the absolute number or percentage of iNKT cells (defined as CD3 + CD14−CD19− Vα24-Jα18 TCR+ cells). However, out of all the iNKT cells, the CD8+ iNKT and CD4−CD8− double-negative (DN) cell percentages steadily increased, while the CD4+ iNKT cell percentages decreased significantly. The mean percentage of CD8+ T cells at all time-points was lower in patients with infections throughout the study. The numbers and percentages of DN iNKT cells were more elevated, considering all time-points, in patients who presented a clinical relapse. FTY may, therefore, exert its beneficial effect in MS patients through various mechanisms, including the increase in Tregs and in iNKT subsets with immunomodulatory potential such as CD8+ iNKT cells. The occurrence of infections was associated with lower mean CD8+ cell counts during treatment with FTY.
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spelling doaj.art-02d12ead33694af9b1f7bb248c7395572023-11-23T07:36:12ZengMDPI AGCells2073-44092021-11-011012332410.3390/cells10123324Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis PatientsDiana Ferraro0Sara De Biasi1Anna Maria Simone2Riccardo Orlandi3Milena Nasi4Francesca Vitetta5Marcello Pinti6Marco Fogliani7Stefano Meletti8Andrea Cossarizza9Patrizia Sola10Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, 41126 Modena, ItalyDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, ItalyNeurology Unit, Ramazzini Hospital, 41012 Carpi, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37129 Verona, ItalyDepartment of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyNeurology Unit, Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, ItalyDepartment of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, ItalyDepartment of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, 41126 Modena, ItalyDepartment of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, 41126 Modena, ItalyDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, ItalyNeurology Unit, Azienda Ospedaliero-Universitaria of Modena, 41126 Modena, ItalyThe altered numbers and functions of cells belonging to immunoregulatory cell networks such as T regulatory (Tregs) and invariant Natural Killer T (iNKT) cells have been reported in Multiple Sclerosis (MS), an immune-mediated disease. We aimed to assess the frequencies of Tregs and iNKT cells in MS patients throughout a one-year treatment with fingolimod (FTY) and to correlate immunological data with efficacy and safety data. The percentage of Tregs (defined as Live Dead-CD3 + CD4 + FoxP3 + CD25++/CD127− cells) increased steadily throughout the year, while there was no significant difference in the absolute number or percentage of iNKT cells (defined as CD3 + CD14−CD19− Vα24-Jα18 TCR+ cells). However, out of all the iNKT cells, the CD8+ iNKT and CD4−CD8− double-negative (DN) cell percentages steadily increased, while the CD4+ iNKT cell percentages decreased significantly. The mean percentage of CD8+ T cells at all time-points was lower in patients with infections throughout the study. The numbers and percentages of DN iNKT cells were more elevated, considering all time-points, in patients who presented a clinical relapse. FTY may, therefore, exert its beneficial effect in MS patients through various mechanisms, including the increase in Tregs and in iNKT subsets with immunomodulatory potential such as CD8+ iNKT cells. The occurrence of infections was associated with lower mean CD8+ cell counts during treatment with FTY.https://www.mdpi.com/2073-4409/10/12/3324multiple sclerosisfingolimodT regulatory cellsiNKT cells
spellingShingle Diana Ferraro
Sara De Biasi
Anna Maria Simone
Riccardo Orlandi
Milena Nasi
Francesca Vitetta
Marcello Pinti
Marco Fogliani
Stefano Meletti
Andrea Cossarizza
Patrizia Sola
Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients
Cells
multiple sclerosis
fingolimod
T regulatory cells
iNKT cells
title Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients
title_full Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients
title_fullStr Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients
title_full_unstemmed Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients
title_short Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients
title_sort modulation of tregs and inkt by fingolimod in multiple sclerosis patients
topic multiple sclerosis
fingolimod
T regulatory cells
iNKT cells
url https://www.mdpi.com/2073-4409/10/12/3324
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