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iNKT Cells in Secondary Progressive Multiple Sclerosis Patients Display Pro-inflammatory Profiles

BACKGROUND: Multiple sclerosis (MS), an autoimmune disease with neurodegeneration and inflammation is characterized by several alterations of different T cell subsets. However, few data exist on the role of iNKT lymphocytes. OBJECTIVE: To identify possible changes in the phenotype of iNKT cells in p...

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Autores principales: De Biasi, Sara, Simone, Anna Maria, Nasi, Milena, Bianchini, Elena, Ferraro, Diana, Vitetta, Francesca, Gibellini, Lara, Pinti, Marcello, Del Giovane, Cinzia, Sola, Patrizia, Cossarizza, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127814/
https://www.ncbi.nlm.nih.gov/pubmed/27965675
http://dx.doi.org/10.3389/fimmu.2016.00555
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author De Biasi, Sara
Simone, Anna Maria
Nasi, Milena
Bianchini, Elena
Ferraro, Diana
Vitetta, Francesca
Gibellini, Lara
Pinti, Marcello
Del Giovane, Cinzia
Sola, Patrizia
Cossarizza, Andrea
author_facet De Biasi, Sara
Simone, Anna Maria
Nasi, Milena
Bianchini, Elena
Ferraro, Diana
Vitetta, Francesca
Gibellini, Lara
Pinti, Marcello
Del Giovane, Cinzia
Sola, Patrizia
Cossarizza, Andrea
author_sort De Biasi, Sara
collection PubMed
description BACKGROUND: Multiple sclerosis (MS), an autoimmune disease with neurodegeneration and inflammation is characterized by several alterations of different T cell subsets. However, few data exist on the role of iNKT lymphocytes. OBJECTIVE: To identify possible changes in the phenotype of iNKT cells in patients with different clinical forms of MS and find alterations in their polyfunctionality [i.e., ability to produce simultaneously up to four cytokines such as IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-4]. METHODS: We studied a total of 165 patients, 91 with a relapsing–remitting form [RR; 31 were treated with interferon (IFN)1a-β, 25 with natalizumab (NAT), 29 with glatiramer acetate; 17 were newly diagnosed RR without treatment, 19 not-active RR without treatment]. Forty-four patients had a progressive MS: 20 primary progressive (PP) and 24 secondary progressive (SP). A total of 55 age- and sex-matched subjects represented healthy controls (CTR). Among fresh peripheral blood mononuclear cells, iNKT cells were identified by flow cytometry. Moreover, the capability of iNKT cells to produce different cytokines (IL-17, TNF-α, IFN-γ, and IL-4) after in vitro stimulation were evaluated in 18 RR (11 treated with NAT and 7 with IFN), 4 PP, 6 SP, and 16 CTR. RESULTS: No main differences were found in iNKT cell phenotype among MS patients with different MS forms or during different treatments. However, the polyfunctional response of iNKT cells showed Th1 and Th17 profiles. This was well evident in patients with SP form, who are characterized by high levels of inflammation and neurodegeneration, and exhibited a sustained increase in the production of Th17 cytokines. Patients treated with NAT displayed lower levels of iNKT cells producing IL-17, TNF-α, and IFN-γ. CONCLUSION: Our data suggest that the progressive phase of the disease is characterized by permanent iNKT activation and a skewing towards an inflammatory phenotype. Compared to other treatments, NAT was able to modulate iNKT cell function.
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spelling pubmed-51278142016-12-13 iNKT Cells in Secondary Progressive Multiple Sclerosis Patients Display Pro-inflammatory Profiles De Biasi, Sara Simone, Anna Maria Nasi, Milena Bianchini, Elena Ferraro, Diana Vitetta, Francesca Gibellini, Lara Pinti, Marcello Del Giovane, Cinzia Sola, Patrizia Cossarizza, Andrea Front Immunol Immunology BACKGROUND: Multiple sclerosis (MS), an autoimmune disease with neurodegeneration and inflammation is characterized by several alterations of different T cell subsets. However, few data exist on the role of iNKT lymphocytes. OBJECTIVE: To identify possible changes in the phenotype of iNKT cells in patients with different clinical forms of MS and find alterations in their polyfunctionality [i.e., ability to produce simultaneously up to four cytokines such as IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-4]. METHODS: We studied a total of 165 patients, 91 with a relapsing–remitting form [RR; 31 were treated with interferon (IFN)1a-β, 25 with natalizumab (NAT), 29 with glatiramer acetate; 17 were newly diagnosed RR without treatment, 19 not-active RR without treatment]. Forty-four patients had a progressive MS: 20 primary progressive (PP) and 24 secondary progressive (SP). A total of 55 age- and sex-matched subjects represented healthy controls (CTR). Among fresh peripheral blood mononuclear cells, iNKT cells were identified by flow cytometry. Moreover, the capability of iNKT cells to produce different cytokines (IL-17, TNF-α, IFN-γ, and IL-4) after in vitro stimulation were evaluated in 18 RR (11 treated with NAT and 7 with IFN), 4 PP, 6 SP, and 16 CTR. RESULTS: No main differences were found in iNKT cell phenotype among MS patients with different MS forms or during different treatments. However, the polyfunctional response of iNKT cells showed Th1 and Th17 profiles. This was well evident in patients with SP form, who are characterized by high levels of inflammation and neurodegeneration, and exhibited a sustained increase in the production of Th17 cytokines. Patients treated with NAT displayed lower levels of iNKT cells producing IL-17, TNF-α, and IFN-γ. CONCLUSION: Our data suggest that the progressive phase of the disease is characterized by permanent iNKT activation and a skewing towards an inflammatory phenotype. Compared to other treatments, NAT was able to modulate iNKT cell function. Frontiers Media S.A. 2016-11-30 /pmc/articles/PMC5127814/ /pubmed/27965675 http://dx.doi.org/10.3389/fimmu.2016.00555 Text en Copyright © 2016 De Biasi, Simone, Nasi, Bianchini, Ferraro, Vitetta, Gibellini, Pinti, Del Giovane, Sola and Cossarizza. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
De Biasi, Sara
Simone, Anna Maria
Nasi, Milena
Bianchini, Elena
Ferraro, Diana
Vitetta, Francesca
Gibellini, Lara
Pinti, Marcello
Del Giovane, Cinzia
Sola, Patrizia
Cossarizza, Andrea
iNKT Cells in Secondary Progressive Multiple Sclerosis Patients Display Pro-inflammatory Profiles
title iNKT Cells in Secondary Progressive Multiple Sclerosis Patients Display Pro-inflammatory Profiles
title_full iNKT Cells in Secondary Progressive Multiple Sclerosis Patients Display Pro-inflammatory Profiles
title_fullStr iNKT Cells in Secondary Progressive Multiple Sclerosis Patients Display Pro-inflammatory Profiles
title_full_unstemmed iNKT Cells in Secondary Progressive Multiple Sclerosis Patients Display Pro-inflammatory Profiles
title_short iNKT Cells in Secondary Progressive Multiple Sclerosis Patients Display Pro-inflammatory Profiles
title_sort inkt cells in secondary progressive multiple sclerosis patients display pro-inflammatory profiles
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127814/
https://www.ncbi.nlm.nih.gov/pubmed/27965675
http://dx.doi.org/10.3389/fimmu.2016.00555
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