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...

Descripción completa

Detalles Bibliográficos
Autores principales: Sugimoto, Chie, Hirotani, Makoto, Yoshikiyo, Kazunori, Koshimizu, Uichi, Wakao, Rika, Horinouchi, Takahiro, Mazaki, Yuichi, Higashi, Tsunehiko, Fukazawa, Toshiyuki, Fujita, Hiroyoshi, Sasaki, Hidenao, Wakao, Hiroshi
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