People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs

Detalhes bibliográficos
Autor(a) principal: Gomes, João Manuel Canto
Data de Publicação: 2023
Outros Autores: Da Silva-Ferreira, Sara, Silva, Carolina S., Boleixa, Daniela, Martins da Silva, Ana, González-Suárez, Inés, Cerqueira, João J., Correia-Neves, Margarida, Nobrega, Claudia
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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spelling 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
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instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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