A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/25855 |
Resumo: | Fonds Wetenschappelijk Onderzoek (G0D6817N) CNPq-FAPESB (PRONEX) VLAIO (PhD scholarship TD) Onderzoeksraad, KU Leuven (IRO) Onderzoeksraad, KU Leuven (Vaast Leysen Leerstoel) |
| id |
CRUZ_4015079543809d8824a1e3a246af9bde |
|---|---|
| oai_identifier_str |
oai:www.arca.fiocruz.br:icict/25855 |
| network_acronym_str |
CRUZ |
| network_name_str |
Repositório Institucional da FIOCRUZ (ARCA) |
| repository_id_str |
2135 |
| spelling |
Cunha, Antonio Ricardo KhouriSantos, Gilvanéia SilvaDierckx, TimMenezes, Soraya MariaDecanine, DanieleTheys, KristofSilva, Aline ClaraVallve, Maria Lourdes FarréBittencourt, Achilea Candida LisboaMangino, MassimoRoederer, MarioVandamme, Anne-MiekeWeyenbergh, Johan Van2018-04-16T14:19:05Z2018-04-16T14:19:05Z2018KHOURI, A. R. et al. A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients. OncoImmunology, e1426423, 2018.2162-4011https://www.arca.fiocruz.br/handle/icict/25855Fonds Wetenschappelijk Onderzoek (G0D6817N) CNPq-FAPESB (PRONEX) VLAIO (PhD scholarship TD) Onderzoeksraad, KU Leuven (IRO) Onderzoeksraad, KU Leuven (Vaast Leysen Leerstoel)University of Leuven. Rega Institute for Medical Research. Department of Microbiology and Immunology. Clinical and Epidemiological Virology. KU Leuven. Leuven, Belgium / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilUniversity of Leuven. Rega Institute for Medical Research. Department of Microbiology and Immunology. Clinical and Epidemiological Virology. KU Leuven. Leuven, BelgiumUniversity of Leuven. Rega Institute for Medical Research. Department of Microbiology and Immunology. Clinical and Epidemiological Virology. KU Leuven. Leuven, BelgiumFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilUniversity of Leuven. Rega Institute for Medical Research. Department of Microbiology and Immunology. Clinical and Epidemiological Virology. KU Leuven. Leuven, BelgiumFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Complexo Hospitalar Universit ario Prof Edgard Santos. Departamento de Pathologia. Salvador, BA, BrasilKing’s College. Department of Twin Research & Genetic Epidemiology. London, UKNational Institute of Allergy and Infectious Diseases. Vaccine Research Center. Immunotechnology Section. Bethesda, MD, USAUniversity of Leuven. Rega Institute for Medical Research. Department of Microbiology and Immunology. Clinical and Epidemiological Virology. KU Leuven. Leuven, Belgium / Universidade Nova de Lisboa. Instituto de Highne e Medicina Tropical. Center for Global Health and Tropical Medicine. Unidade de Microbiologia. Lisbon,University of Leuven. Rega Institute for Medical Research. Department of Microbiology and Immunology. Clinical and Epidemiological Virology. KU Leuven. Leuven, BelgiumAdult T-cell leukemia (ATL) is an aggressive, chemotherapy-resistant CD4CCD25C leukemia caused by HTLV-1 infection, which usually develops in a minority of patients several decades after infection. IFN C AZT combination therapy has shown clinical benefit in ATL, although its mechanism of action remains unclear. We have previously shown that an IFN-responsive FAS promoter polymorphism in a STAT1 binding site (rs1800682) is associated to ATL susceptibility and survival. Recently, CD4 T stem cell memory (TSCM) Fashi cells have been identified as the hierarchical cellular apex of ATL, but a possible link between FAS, apoptosis, proliferation and IFN response in ATL has not been studied. In this study, we found significant ex vivo antiproliferative, antiviral and immunomodulatory effects of IFN-a treatment in short-term culture of primary mononuclear cells from ATL patients (n D 25). Bayesian Network analysis allowed us to integrate ex vivo IFN-a response with clinical, genetic and immunological data from ATL patients, thereby revealing a central role for FAS -670 polymorphism and apoptosis in the coordinated mechanism of action of IFN-a. FAS genotype-dependence of IFN-induced apoptosis was experimentally validated in an independent cohort of healthy controls (n D 20). The same FAS -670 polymorphism also determined CD4 TSCM levels in a genome-wide twin study (p D 7 £ 10¡11, n D 460), confirming a genetic link between apoptosis and TSCM levels. Transcriptomic analysis and cell type deconvolution confirmed the FAS genotype/TSCM link and IFN-a-induced downregulation of CD4 TSCMspecific genes in ATL patient cells. In conclusion, ex vivo IFN-a treatment exerts a pleiotropic effect on primary ATL cells, with a genetic IFN/STAT1/Fas axis determining apoptosis vs. proliferation and underscoring the CD4 TSCM model of ATL leukemogenesis.engTaylor & FrancisCD95HTLV-1GenéticaInterferonLeucemiaLinfomaOncogêneseCD95HTLV-1GeneticsInterferonLeukemiaLymphomaOncogenesisA genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patientsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/25855/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALKhouri R A genetic IFN STAT1 FAS axis determines CD4....pdfKhouri R A genetic IFN STAT1 FAS axis determines CD4....pdfapplication/pdf3750094https://www.arca.fiocruz.br/bitstream/icict/25855/2/Khouri%20R%20A%20genetic%20IFN%20STAT1%20FAS%20axis%20determines%20CD4....pdfc1f8228d9c395392e7f649d64ae9fc0fMD52TEXTKhouri R A genetic IFN STAT1 FAS axis determines CD4....pdf.txtKhouri R A genetic IFN STAT1 FAS axis determines CD4....pdf.txtExtracted texttext/plain66424https://www.arca.fiocruz.br/bitstream/icict/25855/3/Khouri%20R%20A%20genetic%20IFN%20STAT1%20FAS%20axis%20determines%20CD4....pdf.txtf13b5af44cf41453080b9fd66300a34dMD53icict/258552023-03-15 14:34:07.821oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:34:07Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients |
| title |
A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients |
| spellingShingle |
A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients Cunha, Antonio Ricardo Khouri CD95 HTLV-1 Genética Interferon Leucemia Linfoma Oncogênese CD95 HTLV-1 Genetics Interferon Leukemia Lymphoma Oncogenesis |
| title_short |
A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients |
| title_full |
A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients |
| title_fullStr |
A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients |
| title_full_unstemmed |
A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients |
| title_sort |
A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients |
| author |
Cunha, Antonio Ricardo Khouri |
| author_facet |
Cunha, Antonio Ricardo Khouri Santos, Gilvanéia Silva Dierckx, Tim Menezes, Soraya Maria Decanine, Daniele Theys, Kristof Silva, Aline Clara Vallve, Maria Lourdes Farré Bittencourt, Achilea Candida Lisboa Mangino, Massimo Roederer, Mario Vandamme, Anne-Mieke Weyenbergh, Johan Van |
| author_role |
author |
| author2 |
Santos, Gilvanéia Silva Dierckx, Tim Menezes, Soraya Maria Decanine, Daniele Theys, Kristof Silva, Aline Clara Vallve, Maria Lourdes Farré Bittencourt, Achilea Candida Lisboa Mangino, Massimo Roederer, Mario Vandamme, Anne-Mieke Weyenbergh, Johan Van |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Cunha, Antonio Ricardo Khouri Santos, Gilvanéia Silva Dierckx, Tim Menezes, Soraya Maria Decanine, Daniele Theys, Kristof Silva, Aline Clara Vallve, Maria Lourdes Farré Bittencourt, Achilea Candida Lisboa Mangino, Massimo Roederer, Mario Vandamme, Anne-Mieke Weyenbergh, Johan Van |
| dc.subject.other.pt_BR.fl_str_mv |
CD95 HTLV-1 Genética Interferon Leucemia Linfoma Oncogênese |
| topic |
CD95 HTLV-1 Genética Interferon Leucemia Linfoma Oncogênese CD95 HTLV-1 Genetics Interferon Leukemia Lymphoma Oncogenesis |
| dc.subject.en.pt_BR.fl_str_mv |
CD95 HTLV-1 Genetics Interferon Leukemia Lymphoma Oncogenesis |
| description |
Fonds Wetenschappelijk Onderzoek (G0D6817N) CNPq-FAPESB (PRONEX) VLAIO (PhD scholarship TD) Onderzoeksraad, KU Leuven (IRO) Onderzoeksraad, KU Leuven (Vaast Leysen Leerstoel) |
| publishDate |
2018 |
| dc.date.accessioned.fl_str_mv |
2018-04-16T14:19:05Z |
| dc.date.available.fl_str_mv |
2018-04-16T14:19:05Z |
| dc.date.issued.fl_str_mv |
2018 |
| 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 |
KHOURI, A. R. et al. A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients. OncoImmunology, e1426423, 2018. |
| dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/25855 |
| dc.identifier.issn.pt_BR.fl_str_mv |
2162-4011 |
| identifier_str_mv |
KHOURI, A. R. et al. A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients. OncoImmunology, e1426423, 2018. 2162-4011 |
| url |
https://www.arca.fiocruz.br/handle/icict/25855 |
| 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 |
Taylor & Francis |
| publisher.none.fl_str_mv |
Taylor & Francis |
| dc.source.none.fl_str_mv |
reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
| instname_str |
Fundação Oswaldo Cruz (FIOCRUZ) |
| instacron_str |
FIOCRUZ |
| institution |
FIOCRUZ |
| reponame_str |
Repositório Institucional da FIOCRUZ (ARCA) |
| collection |
Repositório Institucional da FIOCRUZ (ARCA) |
| bitstream.url.fl_str_mv |
https://www.arca.fiocruz.br/bitstream/icict/25855/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/25855/2/Khouri%20R%20A%20genetic%20IFN%20STAT1%20FAS%20axis%20determines%20CD4....pdf https://www.arca.fiocruz.br/bitstream/icict/25855/3/Khouri%20R%20A%20genetic%20IFN%20STAT1%20FAS%20axis%20determines%20CD4....pdf.txt |
| bitstream.checksum.fl_str_mv |
5a560609d32a3863062d77ff32785d58 c1f8228d9c395392e7f649d64ae9fc0f f13b5af44cf41453080b9fd66300a34d |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ) |
| repository.mail.fl_str_mv |
repositorio.arca@fiocruz.br |
| _version_ |
1813009307434745856 |