A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation

Brazilian National Research Council (CNPq/Science Without Borders, PVE), Fonds voor Wetenschappelijk Onderzoek (FWO, grant G.0778.10N and G0D6817N).

Detalhes bibliográficos
Autores: Menezes, Soraya Maria, Leal, Fabio Eudes, Dierckx, Tim, Cunha, Antonio Ricardo Khouri, Decanine, Daniele, Santos, Gilvaneia Silva, Schnitman, Saul V., Kruschewsky, Ramon, López, Giovanni, Alvarez, Carolina, Talledo, Michael, Gotuzzo, Eduardo, Nixon, Douglas F., Vercauteren, Jurgen, Brassat, David, Liblau, Roland, Vandamme, Anne Mieke, Castro Filho, Bernardo Galvão, Van Weyenbergh, Johan Josef Roza Maria
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:Brasil
Recursos:Fundação Oswaldo Cruz (FIOCRUZ)
Repositorio:Repositório Institucional da FIOCRUZ (ARCA)
Idioma:inglés
OAI Identifier:oai:arca.fiocruz.br:icict/25404
Acesso em linha:https://arca.fiocruz.br/handle/icict/25404
Access Level:acceso abierto
Palavra-chave:Fas / CD95
Proliferação
Mielopatia associada ao HTLV-1 / paraparesia espástica tropical
Doença linfoproliferativa
Apoptose
Interferão
NF-κB
Esclerose múltipla
Fas/CD95
Proliferation
HTLV-1-associated myelopathy/tropical spastic paraparesis
Lymphoproliferative disease
Apoptosis
Interferon
Multiple sclerosis
03 Saúde e Bem-Estar
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dc.title.none.fl_str_mv A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
title A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
spellingShingle A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
Menezes, Soraya Maria
Fas / CD95
Proliferação
Mielopatia associada ao HTLV-1 / paraparesia espástica tropical
Doença linfoproliferativa
Apoptose
Interferão
NF-κB
Esclerose múltipla
Fas/CD95
Proliferation
HTLV-1-associated myelopathy/tropical spastic paraparesis
Lymphoproliferative disease
Apoptosis
Interferon
NF-κB
Multiple sclerosis
03 Saúde e Bem-Estar
title_short A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
title_full A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
title_fullStr A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
title_full_unstemmed A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
title_sort A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation
dc.creator.none.fl_str_mv Menezes, Soraya Maria
Leal, Fabio Eudes
Dierckx, Tim
Cunha, Antonio Ricardo Khouri
Decanine, Daniele
Santos, Gilvaneia Silva
Schnitman, Saul V.
Kruschewsky, Ramon
López, Giovanni
Alvarez, Carolina
Talledo, Michael
Gotuzzo, Eduardo
Nixon, Douglas F.
Vercauteren, Jurgen
Brassat, David
Liblau, Roland
Vandamme, Anne Mieke
Castro Filho, Bernardo Galvão
Van Weyenbergh, Johan Josef Roza Maria
author Menezes, Soraya Maria
author_facet Menezes, Soraya Maria
Leal, Fabio Eudes
Dierckx, Tim
Cunha, Antonio Ricardo Khouri
Decanine, Daniele
Santos, Gilvaneia Silva
Schnitman, Saul V.
Kruschewsky, Ramon
López, Giovanni
Alvarez, Carolina
Talledo, Michael
Gotuzzo, Eduardo
Nixon, Douglas F.
Vercauteren, Jurgen
Brassat, David
Liblau, Roland
Vandamme, Anne Mieke
Castro Filho, Bernardo Galvão
Van Weyenbergh, Johan Josef Roza Maria
author_role author
author2 Leal, Fabio Eudes
Dierckx, Tim
Cunha, Antonio Ricardo Khouri
Decanine, Daniele
Santos, Gilvaneia Silva
Schnitman, Saul V.
Kruschewsky, Ramon
López, Giovanni
Alvarez, Carolina
Talledo, Michael
Gotuzzo, Eduardo
Nixon, Douglas F.
Vercauteren, Jurgen
Brassat, David
Liblau, Roland
Vandamme, Anne Mieke
Castro Filho, Bernardo Galvão
Van Weyenbergh, Johan Josef Roza Maria
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.other.none.fl_str_mv Fas / CD95
Proliferação
Mielopatia associada ao HTLV-1 / paraparesia espástica tropical
Doença linfoproliferativa
Apoptose
Interferão
NF-κB
Esclerose múltipla
topic Fas / CD95
Proliferação
Mielopatia associada ao HTLV-1 / paraparesia espástica tropical
Doença linfoproliferativa
Apoptose
Interferão
NF-κB
Esclerose múltipla
Fas/CD95
Proliferation
HTLV-1-associated myelopathy/tropical spastic paraparesis
Lymphoproliferative disease
Apoptosis
Interferon
NF-κB
Multiple sclerosis
03 Saúde e Bem-Estar
dc.subject.en.none.fl_str_mv Fas/CD95
Proliferation
HTLV-1-associated myelopathy/tropical spastic paraparesis
Lymphoproliferative disease
Apoptosis
Interferon
NF-κB
Multiple sclerosis
dc.subject.ods.none.fl_str_mv 03 Saúde e Bem-Estar
description Brazilian National Research Council (CNPq/Science Without Borders, PVE), Fonds voor Wetenschappelijk Onderzoek (FWO, grant G.0778.10N and G0D6817N).
publishDate 2017
dc.date.issued.fl_str_mv 2017
dc.date.accessioned.fl_str_mv 2018-03-19T19:20:43Z
dc.date.available.fl_str_mv 2018-03-19T19:20:43Z
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.citation.fl_str_mv MENEZES, S. M. et al. A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation. Frontiers in Immunology, v. 8, p. 97, 2017.
dc.identifier.uri.fl_str_mv https://arca.fiocruz.br/handle/icict/25404
dc.identifier.issn.none.fl_str_mv 1664-3224
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2017.00097
identifier_str_mv MENEZES, S. M. et al. A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation. Frontiers in Immunology, v. 8, p. 97, 2017.
1664-3224
10.3389/fimmu.2017.00097
url https://arca.fiocruz.br/handle/icict/25404
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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spelling 2018-03-19T19:20:43Z2018-03-19T19:20:43Z2017MENEZES, S. M. et al. A FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation. Frontiers in Immunology, v. 8, p. 97, 2017.1664-3224https://arca.fiocruz.br/handle/icict/2540410.3389/fimmu.2017.00097Brazilian National Research Council (CNPq/Science Without Borders, PVE), Fonds voor Wetenschappelijk Onderzoek (FWO, grant G.0778.10N and G0D6817N).Rega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, BelgiumThe George Washington University. Immunology & Tropical Medicine Department of Microbiology. Washington, DC, USARega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, BelgiumRega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Enfermidades Infecciosas Transmitidas por Vetores. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Enfermidades Infecciosas Transmitidas por Vetores. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Enfermidades Infecciosas Transmitidas por Vetores. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Enfermidades Infecciosas Transmitidas por Vetores. Salvador, BA, BrasilBahiana School of Medicine and Public Health. Salvador, BA, BrazilUniversidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander von Humboldt. Lima, PeruRega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium / Universidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander von Humboldt. Lima, PeruUniversidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander von Humboldt. Lima, PeruUniversidad Peruana Cayetano Heredia. Instituto de Medicina Tropical Alexander von Humboldt. Lima, Peru / Hospital Cayetano Heredia. Departamento de Enfermedades Infecciosas,Tropicales y Dermatológicas. Lima, PeruThe George Washington University. Immunology & Tropical Medicine Department of Microbiology. Washington, DC, USARega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, BelgiumUniversité de Toulouse. Hôpital Purpan. Inserm and Pôle des Neurosciences. Toulouse, FranceUniversité de Toulouse. Hôpital Purpan. Inserm and Pôle des Neurosciences. Toulouse, FranceRega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium / Universidade Nova de Lisboa. Instituto de Higiene e Medicina Tropical. Center for Global Health and Tropical Medicine. Unidade de Microbiologia. Lisbon, PortugalBahiana School of Medicine and Public Health. Salvador, BA, BrazilRega Institute for Medical Research. Clinical and Epidemiological Virology. Department of Microbiology and Immunology. KU Leuven, Leuven, BelgiumHuman T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functionalFAS-670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. FashiT stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, bothFASandSTAT1have been identified in an IFN-inducible HAM/TSP gene signature, but its pathobiological significance remains unclear. We comprehensively explored Fas expression (protein/mRNA) and function in lymphocyte activation, apoptosis, proliferation, and transcriptome, in PBMC from a total of 47 HAM/TSP patients, 40 asymptomatic HTLV-1-infected individuals (AC), and 58 HTLV-1 -uninfected healthy controls. Fas surface expression followed a two-step increase from HC to AC and from AC to HAM/TSP. In HAM/TSP, Fas levels correlated positively to lymphocyte activation markers, but negatively to age of onset, linking Fashicells to earlier, more aggressive disease. Surprisingly, increased lymphocyte Fas expression in HAM/TSP was linked to decreased apoptosis and increased lymphoproliferation uponin vitroculture, but not to proviral load. This Fashiphenotype is HAM/TSP-specific, since bothex vivoandin vitroFas expression was increased as compared to multiple sclerosis (MS), another neuroinflammatory disorder. To elucidate the molecular mechanism underlying non-apoptotic Fas signaling in HAM/TSP, we combined transcriptome analysis with functional assays, i.e., blocking vs. triggering Fas receptorin vitrowith antagonist and agonist-, anti-Fas mAb, respectively. Treatment with agonist anti-Fas mAb restored apoptosis, indicating biased, but not defective Fas signaling in HAM/TSP.In silicoanalysis revealed biased Fas signaling toward proliferation and inflammation, driven by RelA/NF-κB. Correlation of Fas transcript levels with proliferation (but not apoptosis) was confirmed in HAM/TSPex vivotranscriptomes. In conclusion, we demonstrated a two-step increase in Fas expression, revealing a unique Fashilymphocyte phenotype in HAM/TSP, distinguishable from MS. Non-apoptotic Fas signaling might fuel HAM/TSP pathogenesis, through increased lymphoproliferation, inflammation, and early age of onset.engFrontiers MediaFas / CD95ProliferaçãoMielopatia associada ao HTLV-1 / paraparesia espástica tropicalDoença linfoproliferativaApoptoseInterferãoNF-κBEsclerose múltiplaFas/CD95ProliferationHTLV-1-associated myelopathy/tropical spastic paraparesisLymphoproliferative diseaseApoptosisInterferonNF-κBMultiple sclerosis03 Saúde e Bem-EstarA FashiLymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZMenezes, Soraya MariaLeal, Fabio EudesDierckx, TimCunha, Antonio Ricardo KhouriDecanine, DanieleSantos, Gilvaneia SilvaSchnitman, Saul V.Kruschewsky, RamonLópez, GiovanniAlvarez, CarolinaTalledo, MichaelGotuzzo, EduardoNixon, Douglas F.Vercauteren, JurgenBrassat, DavidLiblau, RolandVandamme, Anne MiekeCastro Filho, Bernardo GalvãoVan Weyenbergh, Johan Josef Roza MariaLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://arca.fiocruz.br/bitstreams/d2e0d1c0-0511-479a-b05f-5751d0510a60/download5a560609d32a3863062d77ff32785d58MD51falseAnonymousREADORIGINALMenezes SM A Fashi Lymphoproliferative Phenotype .......pdfMenezes SM A Fashi Lymphoproliferative Phenotype .......pdfapplication/pdf2005058https://arca.fiocruz.br/bitstreams/a668cb89-07c4-413f-b690-63a568c7d45d/downloade358a97eae53690edb96d33e61a9f9afMD52trueAnonymousREADTEXTMenezes SM A Fashi Lymphoproliferative Phenotype .......pdf.txtMenezes SM A Fashi Lymphoproliferative Phenotype .......pdf.txtExtracted texttext/plain65809https://arca.fiocruz.br/bitstreams/723cd5d9-c965-4bca-9d40-9e820f58393e/download948b579afb199f9b98ed40101db3a113MD511falseAnonymousREADTHUMBNAILMenezes SM A Fashi Lymphoproliferative Phenotype .......pdf.jpgMenezes SM A Fashi Lymphoproliferative Phenotype .......pdf.jpgGenerated Thumbnailimage/jpeg42562https://arca.fiocruz.br/bitstreams/0b45e291-5d5d-4343-9100-5fdf6e964b50/downloadc22881ddc5cc2dbfc7b416a3485490b8MD512falseAnonymousREADicict/254042025-12-10 14:31:58.973open.accessoai:arca.fiocruz.br:icict/25404https://arca.fiocruz.brRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352025-12-10T17:31:58Repositório Institucional da FIOCRUZ (ARCA) - 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score 15.198674

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