People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/85181 |
Resumo: | The importance of circulating immune cells to primary progressive multiple sclerosis (PPMS) pathophysiology is still controversial because most immunotherapies were shown to be ineffective in treating people with PPMS (pwPPMS). Yet, although controversial, data exist describing peripheral immune system alterations in pwPPMS. This study aims to investigate which alterations might be present in pwPPMS free of disease-modifying drugs (DMD) in comparison to age- and sex-matched healthy controls. A multicentric cross-sectional study was performed using 23 pwPPMS and 23 healthy controls. The phenotype of conventional CD4<sup>+</sup> and CD8<sup>+</sup> T cells, regulatory T cells (Tregs), B cells, natural killer (NK) T cells and NK cells was assessed. Lower numbers of central memory CD4<sup>+</sup> and CD8<sup>+</sup> T cells and activated HLA-DR<sup>+</sup> Tregs were observed in pwPPMS. Regarding NK and NKT cells, pwPPMS presented higher percentages of CD56<sup>dim</sup>CD57<sup>+</sup> NK cells expressing NKp46 and of NKT cells expressing KIR2DL2/3 and NKp30. Higher disease severity scores and an increasing time since diagnosis was correlated with lower numbers of inhibitory NK cells subsets. Our findings contribute to reinforcing the hypotheses that alterations in peripheral immune cells are present in pwPPMS and that changes in NK cell populations are the strongest correlate of disease severity. |
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People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ TregsPrimary progressive multiple sclerosisT cellRegulatory T cell (Treg)NK cellNKT cellB cellScience & TechnologyThe importance of circulating immune cells to primary progressive multiple sclerosis (PPMS) pathophysiology is still controversial because most immunotherapies were shown to be ineffective in treating people with PPMS (pwPPMS). Yet, although controversial, data exist describing peripheral immune system alterations in pwPPMS. This study aims to investigate which alterations might be present in pwPPMS free of disease-modifying drugs (DMD) in comparison to age- and sex-matched healthy controls. A multicentric cross-sectional study was performed using 23 pwPPMS and 23 healthy controls. The phenotype of conventional CD4<sup>+</sup> and CD8<sup>+</sup> T cells, regulatory T cells (Tregs), B cells, natural killer (NK) T cells and NK cells was assessed. Lower numbers of central memory CD4<sup>+</sup> and CD8<sup>+</sup> T cells and activated HLA-DR<sup>+</sup> Tregs were observed in pwPPMS. Regarding NK and NKT cells, pwPPMS presented higher percentages of CD56<sup>dim</sup>CD57<sup>+</sup> NK cells expressing NKp46 and of NKT cells expressing KIR2DL2/3 and NKp30. Higher disease severity scores and an increasing time since diagnosis was correlated with lower numbers of inhibitory NK cells subsets. Our findings contribute to reinforcing the hypotheses that alterations in peripheral immune cells are present in pwPPMS and that changes in NK cell populations are the strongest correlate of disease severity.This work has been funded by a research grant from the Academic Clinical Center of the Hospital of Braga; by national funds through the Foundation for Science and Technology (FCT) (UIDB/50026/2020 and UIDP/50026/2020); and by the project NORTE-01-0145-FEDER-000039, supported by the Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). J.C.-G. has been supported by FCT PhD grants (PD/BD/137433/2018 and COVID/BD/152629/2022). C.S. has been supported by an FCT PhD grant (PD/BDE/142976/2018).Multidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoGomes, João Manuel CantoDa Silva-Ferreira, SaraSilva, Carolina S.Boleixa, DanielaMartins da Silva, AnaGonzález-Suárez, InésCerqueira, João J.Correia-Neves, MargaridaNobrega, Claudia2023-01-292023-01-29T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/85181engCanto-Gomes, J.; Da Silva-Ferreira, S.; Silva, C.S.; Boleixa, D.; Martins da Silva, A.; González-Suárez, I.; Cerqueira, J.J.; Correia-Neves, M.; Nobrega, C. People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR+ Tregs. Cells 2023, 12, 439. https://doi.org/10.3390/cells120304392073-440910.3390/cells1203043936766781439https://www.mdpi.com/2073-4409/12/3/439info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-23T01:29:19Zoai:repositorium.sdum.uminho.pt:1822/85181Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:04:46.299423Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs |
title |
People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs |
spellingShingle |
People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs Gomes, João Manuel Canto Primary progressive multiple sclerosis T cell Regulatory T cell (Treg) NK cell NKT cell B cell Science & Technology |
title_short |
People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs |
title_full |
People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs |
title_fullStr |
People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs |
title_full_unstemmed |
People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs |
title_sort |
People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs |
author |
Gomes, João Manuel Canto |
author_facet |
Gomes, João Manuel Canto Da Silva-Ferreira, Sara Silva, Carolina S. Boleixa, Daniela Martins da Silva, Ana González-Suárez, Inés Cerqueira, João J. Correia-Neves, Margarida Nobrega, Claudia |
author_role |
author |
author2 |
Da Silva-Ferreira, Sara Silva, Carolina S. Boleixa, Daniela Martins da Silva, Ana González-Suárez, Inés Cerqueira, João J. Correia-Neves, Margarida Nobrega, Claudia |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Gomes, João Manuel Canto Da Silva-Ferreira, Sara Silva, Carolina S. Boleixa, Daniela Martins da Silva, Ana González-Suárez, Inés Cerqueira, João J. Correia-Neves, Margarida Nobrega, Claudia |
dc.subject.por.fl_str_mv |
Primary progressive multiple sclerosis T cell Regulatory T cell (Treg) NK cell NKT cell B cell Science & Technology |
topic |
Primary progressive multiple sclerosis T cell Regulatory T cell (Treg) NK cell NKT cell B cell Science & Technology |
description |
The importance of circulating immune cells to primary progressive multiple sclerosis (PPMS) pathophysiology is still controversial because most immunotherapies were shown to be ineffective in treating people with PPMS (pwPPMS). Yet, although controversial, data exist describing peripheral immune system alterations in pwPPMS. This study aims to investigate which alterations might be present in pwPPMS free of disease-modifying drugs (DMD) in comparison to age- and sex-matched healthy controls. A multicentric cross-sectional study was performed using 23 pwPPMS and 23 healthy controls. The phenotype of conventional CD4<sup>+</sup> and CD8<sup>+</sup> T cells, regulatory T cells (Tregs), B cells, natural killer (NK) T cells and NK cells was assessed. Lower numbers of central memory CD4<sup>+</sup> and CD8<sup>+</sup> T cells and activated HLA-DR<sup>+</sup> Tregs were observed in pwPPMS. Regarding NK and NKT cells, pwPPMS presented higher percentages of CD56<sup>dim</sup>CD57<sup>+</sup> NK cells expressing NKp46 and of NKT cells expressing KIR2DL2/3 and NKp30. Higher disease severity scores and an increasing time since diagnosis was correlated with lower numbers of inhibitory NK cells subsets. Our findings contribute to reinforcing the hypotheses that alterations in peripheral immune cells are present in pwPPMS and that changes in NK cell populations are the strongest correlate of disease severity. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-01-29 2023-01-29T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/1822/85181 |
url |
https://hdl.handle.net/1822/85181 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Canto-Gomes, J.; Da Silva-Ferreira, S.; Silva, C.S.; Boleixa, D.; Martins da Silva, A.; González-Suárez, I.; Cerqueira, J.J.; Correia-Neves, M.; Nobrega, C. People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR+ Tregs. Cells 2023, 12, 439. https://doi.org/10.3390/cells12030439 2073-4409 10.3390/cells12030439 36766781 439 https://www.mdpi.com/2073-4409/12/3/439 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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