Cargando…
The dynamics of mucosal-associated invariant T cells in multiple sclerosis
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination, gliosis and axonal loss in the Central Nervous System. Although the etiology of the disease has remained enigmatic, recent studies have suggested a role of the innate-like T cells, called Mucosa...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974206/ https://www.ncbi.nlm.nih.gov/pubmed/27536542 http://dx.doi.org/10.1186/s40064-016-2923-9 |
_version_ | 1782446511527821312 |
---|---|
author | Sugimoto, Chie Hirotani, Makoto Yoshikiyo, Kazunori Koshimizu, Uichi Wakao, Rika Horinouchi, Takahiro Mazaki, Yuichi Higashi, Tsunehiko Fukazawa, Toshiyuki Fujita, Hiroyoshi Sasaki, Hidenao Wakao, Hiroshi |
author_facet | Sugimoto, Chie Hirotani, Makoto Yoshikiyo, Kazunori Koshimizu, Uichi Wakao, Rika Horinouchi, Takahiro Mazaki, Yuichi Higashi, Tsunehiko Fukazawa, Toshiyuki Fujita, Hiroyoshi Sasaki, Hidenao Wakao, Hiroshi |
author_sort | Sugimoto, Chie |
collection | PubMed |
description | BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination, gliosis and axonal loss in the Central Nervous System. Although the etiology of the disease has remained enigmatic, recent studies have suggested a role of the innate-like T cells, called Mucosal Associated Invariant T cells (MAITs) in the pathophysiology. In the present study, we have analyzed the relative frequency of MAITs and the expression of the cell surface antigens in MAITs to seek a possible link to the disease. RESULTS: There was little difference in the frequency of total MAITs between healthy donors (HDs) and untreated MS patients, whereas the latter harbored more CD8(lo/neg) (DN) MAITs concomitant with a decrease in CD8(high) MAITs and in CD4 MAITs compared with those in HDs. While the expression of CCR5, CCR6, CD95, CD127, and CD150 has increased in untreated subjects compared with that in HDs, CD45RO has declined in untreated subjects in both DN MAITs and CD8(hi) MAITs. FTY720 therapy has increased the relative frequency of total MAITs in a time-dependent fashion up to 2 years. Intriguingly, FTY720 therapy for 3 years reversed the above phenotype, engendering more CD8(high) MAITs accompanied with decreased DN MAITs. FTY720 therapy affected the cytokine production from CD4 T cells and also enhanced the relative frequency of cells producing both TNF-α and IFN-γ from MAITs, CD8 T cells, and CD4 T cells compared with that in untreated subjects. CONCLUSIONS: FTY 720 therapy enhanced the relative frequency of MAITs in MS patients in a time-dependent manner. Although the expression of CD8 in MAITs has been affected early by FTY720, longer treatment has reversed the phenotypic change. These data demonstrated that FTY720 induced dynamic change in the relative frequency and in the phenotype of MAITs in MS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-2923-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4974206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-49742062016-08-17 The dynamics of mucosal-associated invariant T cells in multiple sclerosis Sugimoto, Chie Hirotani, Makoto Yoshikiyo, Kazunori Koshimizu, Uichi Wakao, Rika Horinouchi, Takahiro Mazaki, Yuichi Higashi, Tsunehiko Fukazawa, Toshiyuki Fujita, Hiroyoshi Sasaki, Hidenao Wakao, Hiroshi Springerplus Research BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination, gliosis and axonal loss in the Central Nervous System. Although the etiology of the disease has remained enigmatic, recent studies have suggested a role of the innate-like T cells, called Mucosal Associated Invariant T cells (MAITs) in the pathophysiology. In the present study, we have analyzed the relative frequency of MAITs and the expression of the cell surface antigens in MAITs to seek a possible link to the disease. RESULTS: There was little difference in the frequency of total MAITs between healthy donors (HDs) and untreated MS patients, whereas the latter harbored more CD8(lo/neg) (DN) MAITs concomitant with a decrease in CD8(high) MAITs and in CD4 MAITs compared with those in HDs. While the expression of CCR5, CCR6, CD95, CD127, and CD150 has increased in untreated subjects compared with that in HDs, CD45RO has declined in untreated subjects in both DN MAITs and CD8(hi) MAITs. FTY720 therapy has increased the relative frequency of total MAITs in a time-dependent fashion up to 2 years. Intriguingly, FTY720 therapy for 3 years reversed the above phenotype, engendering more CD8(high) MAITs accompanied with decreased DN MAITs. FTY720 therapy affected the cytokine production from CD4 T cells and also enhanced the relative frequency of cells producing both TNF-α and IFN-γ from MAITs, CD8 T cells, and CD4 T cells compared with that in untreated subjects. CONCLUSIONS: FTY 720 therapy enhanced the relative frequency of MAITs in MS patients in a time-dependent manner. Although the expression of CD8 in MAITs has been affected early by FTY720, longer treatment has reversed the phenotypic change. These data demonstrated that FTY720 induced dynamic change in the relative frequency and in the phenotype of MAITs in MS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-2923-9) contains supplementary material, which is available to authorized users. Springer International Publishing 2016-08-05 /pmc/articles/PMC4974206/ /pubmed/27536542 http://dx.doi.org/10.1186/s40064-016-2923-9 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Sugimoto, Chie Hirotani, Makoto Yoshikiyo, Kazunori Koshimizu, Uichi Wakao, Rika Horinouchi, Takahiro Mazaki, Yuichi Higashi, Tsunehiko Fukazawa, Toshiyuki Fujita, Hiroyoshi Sasaki, Hidenao Wakao, Hiroshi The dynamics of mucosal-associated invariant T cells in multiple sclerosis |
title | The dynamics of mucosal-associated invariant T cells in multiple sclerosis |
title_full | The dynamics of mucosal-associated invariant T cells in multiple sclerosis |
title_fullStr | The dynamics of mucosal-associated invariant T cells in multiple sclerosis |
title_full_unstemmed | The dynamics of mucosal-associated invariant T cells in multiple sclerosis |
title_short | The dynamics of mucosal-associated invariant T cells in multiple sclerosis |
title_sort | dynamics of mucosal-associated invariant t cells in multiple sclerosis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974206/ https://www.ncbi.nlm.nih.gov/pubmed/27536542 http://dx.doi.org/10.1186/s40064-016-2923-9 |
work_keys_str_mv | AT sugimotochie thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT hirotanimakoto thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT yoshikiyokazunori thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT koshimizuuichi thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT wakaorika thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT horinouchitakahiro thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT mazakiyuichi thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT higashitsunehiko thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT fukazawatoshiyuki thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT fujitahiroyoshi thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT sasakihidenao thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT wakaohiroshi thedynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT sugimotochie dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT hirotanimakoto dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT yoshikiyokazunori dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT koshimizuuichi dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT wakaorika dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT horinouchitakahiro dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT mazakiyuichi dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT higashitsunehiko dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT fukazawatoshiyuki dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT fujitahiroyoshi dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT sasakihidenao dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis AT wakaohiroshi dynamicsofmucosalassociatedinvarianttcellsinmultiplesclerosis |