Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients

Bibliographic Details
Main Author: Amaral-Silva, Daniela
Publication Date: 2021
Other Authors: Gonçalves, Rute, Torrão, Rita C., Torres, Rita, Falcão, Sandra, Gonçalves, Maria João, Araújo, Maria Paula, Martins, Maria José, Lopes, Carina, Neto, Agna, Marona, José, Costa, Tiago, Castelão, Walter, Silva, Ana Bento, Silva, Inês, Lourenço, Maria Helena, Mateus, Margarida, Gonçalves, Nuno Pina, Manica, Santiago, Costa, Manuela, Pimentel-Santos, F. M., Mourão, Ana Filipa, Branco, Jaime, Soares, Helena
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/127059
Summary: Funding Information: We thank Cláudia Andrade for technical support and Juliana Gonçalves for testing samples for SARS-CoV-2 exposure. We are extremely grateful to all the participants of the study and to the whole rheumatology department at Hospital Egas Moniz that made this study possible. This work was supported by Fundação para a Ciência e Tecnologia (FCT) PTDC/MEC-REU/29520/2017, by iNOVA4Health UID/Multi/04462 and by Portuguese Society for Rheumatology (SPR) grants to H.S. H.S. is supported by FCT through IF/01722/2013 and CEECIND/01049/2020, DAS and RCT were supported by FCT through PD/BD/137409/2018 and UID/Multi/04462, respectively. Publisher Copyright: © 2021, The Author(s).
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spelling Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patientsMedicine (miscellaneous)Biochemistry, Genetics and Molecular Biology(all)Agricultural and Biological Sciences(all)Funding Information: We thank Cláudia Andrade for technical support and Juliana Gonçalves for testing samples for SARS-CoV-2 exposure. We are extremely grateful to all the participants of the study and to the whole rheumatology department at Hospital Egas Moniz that made this study possible. This work was supported by Fundação para a Ciência e Tecnologia (FCT) PTDC/MEC-REU/29520/2017, by iNOVA4Health UID/Multi/04462 and by Portuguese Society for Rheumatology (SPR) grants to H.S. H.S. is supported by FCT through IF/01722/2013 and CEECIND/01049/2020, DAS and RCT were supported by FCT through PD/BD/137409/2018 and UID/Multi/04462, respectively. Publisher Copyright: © 2021, The Author(s).CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program.iNOVA4Health - pólo NMSCentro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Comprehensive Health Research Centre (CHRC) - pólo NMSRUNAmaral-Silva, DanielaGonçalves, RuteTorrão, Rita C.Torres, RitaFalcão, SandraGonçalves, Maria JoãoAraújo, Maria PaulaMartins, Maria JoséLopes, CarinaNeto, AgnaMarona, JoséCosta, TiagoCastelão, WalterSilva, Ana BentoSilva, InêsLourenço, Maria HelenaMateus, MargaridaGonçalves, Nuno PinaManica, SantiagoCosta, ManuelaPimentel-Santos, F. M.Mourão, Ana FilipaBranco, JaimeSoares, Helena2021-11-03T05:02:41Z2021-09-272021-09-27T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/127059engPURE: 34142447https://doi.org/10.1038/s42003-021-02659-0info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-09-23T01:38:10Zoai:run.unl.pt:10362/127059Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:27:57.923557Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients
title Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients
spellingShingle Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients
Amaral-Silva, Daniela
Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
title_short Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients
title_full Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients
title_fullStr Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients
title_full_unstemmed Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients
title_sort Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients
author Amaral-Silva, Daniela
author_facet Amaral-Silva, Daniela
Gonçalves, Rute
Torrão, Rita C.
Torres, Rita
Falcão, Sandra
Gonçalves, Maria João
Araújo, Maria Paula
Martins, Maria José
Lopes, Carina
Neto, Agna
Marona, José
Costa, Tiago
Castelão, Walter
Silva, Ana Bento
Silva, Inês
Lourenço, Maria Helena
Mateus, Margarida
Gonçalves, Nuno Pina
Manica, Santiago
Costa, Manuela
Pimentel-Santos, F. M.
Mourão, Ana Filipa
Branco, Jaime
Soares, Helena
author_role author
author2 Gonçalves, Rute
Torrão, Rita C.
Torres, Rita
Falcão, Sandra
Gonçalves, Maria João
Araújo, Maria Paula
Martins, Maria José
Lopes, Carina
Neto, Agna
Marona, José
Costa, Tiago
Castelão, Walter
Silva, Ana Bento
Silva, Inês
Lourenço, Maria Helena
Mateus, Margarida
Gonçalves, Nuno Pina
Manica, Santiago
Costa, Manuela
Pimentel-Santos, F. M.
Mourão, Ana Filipa
Branco, Jaime
Soares, Helena
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv iNOVA4Health - pólo NMS
Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Comprehensive Health Research Centre (CHRC) - pólo NMS
RUN
dc.contributor.author.fl_str_mv Amaral-Silva, Daniela
Gonçalves, Rute
Torrão, Rita C.
Torres, Rita
Falcão, Sandra
Gonçalves, Maria João
Araújo, Maria Paula
Martins, Maria José
Lopes, Carina
Neto, Agna
Marona, José
Costa, Tiago
Castelão, Walter
Silva, Ana Bento
Silva, Inês
Lourenço, Maria Helena
Mateus, Margarida
Gonçalves, Nuno Pina
Manica, Santiago
Costa, Manuela
Pimentel-Santos, F. M.
Mourão, Ana Filipa
Branco, Jaime
Soares, Helena
dc.subject.por.fl_str_mv Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
topic Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
description Funding Information: We thank Cláudia Andrade for technical support and Juliana Gonçalves for testing samples for SARS-CoV-2 exposure. We are extremely grateful to all the participants of the study and to the whole rheumatology department at Hospital Egas Moniz that made this study possible. This work was supported by Fundação para a Ciência e Tecnologia (FCT) PTDC/MEC-REU/29520/2017, by iNOVA4Health UID/Multi/04462 and by Portuguese Society for Rheumatology (SPR) grants to H.S. H.S. is supported by FCT through IF/01722/2013 and CEECIND/01049/2020, DAS and RCT were supported by FCT through PD/BD/137409/2018 and UID/Multi/04462, respectively. Publisher Copyright: © 2021, The Author(s).
publishDate 2021
dc.date.none.fl_str_mv 2021-11-03T05:02:41Z
2021-09-27
2021-09-27T00:00:00Z
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 http://hdl.handle.net/10362/127059
url http://hdl.handle.net/10362/127059
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PURE: 34142447
https://doi.org/10.1038/s42003-021-02659-0
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.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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