PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies whose production is promoted by autoreactive T follicular helper (TFH) cells. During SLE pathogenesis, basophils accumulate in secondary lymphoid organs (SLO), amplify autoantibody production and...

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Autores: Tchen, John, Simon, Quentin|||0000-0002-2383-2809, Chapart, Léa|||0009-0008-9720-1146, Thaminy, Morgane K.|||0009-0002-4842-0277, Vibhushan, Shamila|||0000-0001-6196-2295, Saveanu, Loredana|||0000-0003-3138-7968, Lamri, Yasmine, Saidoune, Fanny, Pacreau, Emeline, Pellefigues, Christophe|||0000-0001-7036-0763, Bex-coudrat, Julie, Karasuyama, Hajime|||0000-0003-0689-0836, Miyake, Kensuke|||0000-0003-1149-3755, Hidalgo Pareja, Juan|||0000-0003-0921-1122, Fallon, Padraic G.|||0000-0002-8401-7293, Papo, Thomas, Blank, Ulrich|||0000-0002-2661-2983, Benhamou, Marc, Hanouna, Guillaume, Sacre, Karim|||0000-0002-6544-234X, Daugas, Eric, Charles, Nicolas|||0000-0002-5416-5834
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:310540
Acesso em linha:https://ddd.uab.cat/record/310540
https://dx.doi.org/urn:doi:10.1038/s41467-024-47691-w
Access Level:acceso abierto
Palavra-chave:Autoimmunity
Basophils
Translational immunology
Lupus nephritis
Germinal centres
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spelling PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupusTchen, JohnSimon, Quentin|||0000-0002-2383-2809Chapart, Léa|||0009-0008-9720-1146Thaminy, Morgane K.|||0009-0002-4842-0277Vibhushan, Shamila|||0000-0001-6196-2295Saveanu, Loredana|||0000-0003-3138-7968Lamri, YasmineSaidoune, FannyPacreau, EmelinePellefigues, Christophe|||0000-0001-7036-0763Bex-coudrat, JulieKarasuyama, Hajime|||0000-0003-0689-0836Miyake, Kensuke|||0000-0003-1149-3755Hidalgo Pareja, Juan|||0000-0003-0921-1122Fallon, Padraic G.|||0000-0002-8401-7293Papo, ThomasBlank, Ulrich|||0000-0002-2661-2983Benhamou, MarcHanouna, GuillaumeSacre, Karim|||0000-0002-6544-234XDaugas, EricCharles, Nicolas|||0000-0002-5416-5834AutoimmunityBasophilsTranslational immunologyLupus nephritisGerminal centresSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies whose production is promoted by autoreactive T follicular helper (TFH) cells. During SLE pathogenesis, basophils accumulate in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms that remain to be defined. Here, we provide evidence for a direct functional relationship between TFH cells and basophils during lupus pathogenesis, both in humans and mice. PD-L1 upregulation on basophils and IL-4 production are associated with TFH and TFH2 cell expansions and with disease activity. Pathogenic TFH cell accumulation, maintenance, and function in SLO were dependent on PD-L1 and IL-4 in basophils, which induced a transcriptional program allowing TFH2 cell differentiation and function. Our study establishes a direct mechanistic link between basophils and TFH cells in SLE that promotes autoantibody production and lupus nephritis. 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/310540https://dx.doi.org/urn:doi:10.1038/s41467-024-47691-wreponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-101105-B-I00open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3105402026-06-06T12:50:31Z
dc.title.none.fl_str_mv PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
title PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
spellingShingle PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
Tchen, John
Autoimmunity
Basophils
Translational immunology
Lupus nephritis
Germinal centres
title_short PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
title_full PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
title_fullStr PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
title_full_unstemmed PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
title_sort PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
dc.creator.none.fl_str_mv Tchen, John
Simon, Quentin|||0000-0002-2383-2809
Chapart, Léa|||0009-0008-9720-1146
Thaminy, Morgane K.|||0009-0002-4842-0277
Vibhushan, Shamila|||0000-0001-6196-2295
Saveanu, Loredana|||0000-0003-3138-7968
Lamri, Yasmine
Saidoune, Fanny
Pacreau, Emeline
Pellefigues, Christophe|||0000-0001-7036-0763
Bex-coudrat, Julie
Karasuyama, Hajime|||0000-0003-0689-0836
Miyake, Kensuke|||0000-0003-1149-3755
Hidalgo Pareja, Juan|||0000-0003-0921-1122
Fallon, Padraic G.|||0000-0002-8401-7293
Papo, Thomas
Blank, Ulrich|||0000-0002-2661-2983
Benhamou, Marc
Hanouna, Guillaume
Sacre, Karim|||0000-0002-6544-234X
Daugas, Eric
Charles, Nicolas|||0000-0002-5416-5834
author Tchen, John
author_facet Tchen, John
Simon, Quentin|||0000-0002-2383-2809
Chapart, Léa|||0009-0008-9720-1146
Thaminy, Morgane K.|||0009-0002-4842-0277
Vibhushan, Shamila|||0000-0001-6196-2295
Saveanu, Loredana|||0000-0003-3138-7968
Lamri, Yasmine
Saidoune, Fanny
Pacreau, Emeline
Pellefigues, Christophe|||0000-0001-7036-0763
Bex-coudrat, Julie
Karasuyama, Hajime|||0000-0003-0689-0836
Miyake, Kensuke|||0000-0003-1149-3755
Hidalgo Pareja, Juan|||0000-0003-0921-1122
Fallon, Padraic G.|||0000-0002-8401-7293
Papo, Thomas
Blank, Ulrich|||0000-0002-2661-2983
Benhamou, Marc
Hanouna, Guillaume
Sacre, Karim|||0000-0002-6544-234X
Daugas, Eric
Charles, Nicolas|||0000-0002-5416-5834
author_role author
author2 Simon, Quentin|||0000-0002-2383-2809
Chapart, Léa|||0009-0008-9720-1146
Thaminy, Morgane K.|||0009-0002-4842-0277
Vibhushan, Shamila|||0000-0001-6196-2295
Saveanu, Loredana|||0000-0003-3138-7968
Lamri, Yasmine
Saidoune, Fanny
Pacreau, Emeline
Pellefigues, Christophe|||0000-0001-7036-0763
Bex-coudrat, Julie
Karasuyama, Hajime|||0000-0003-0689-0836
Miyake, Kensuke|||0000-0003-1149-3755
Hidalgo Pareja, Juan|||0000-0003-0921-1122
Fallon, Padraic G.|||0000-0002-8401-7293
Papo, Thomas
Blank, Ulrich|||0000-0002-2661-2983
Benhamou, Marc
Hanouna, Guillaume
Sacre, Karim|||0000-0002-6544-234X
Daugas, Eric
Charles, Nicolas|||0000-0002-5416-5834
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Autoimmunity
Basophils
Translational immunology
Lupus nephritis
Germinal centres
topic Autoimmunity
Basophils
Translational immunology
Lupus nephritis
Germinal centres
description Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies whose production is promoted by autoreactive T follicular helper (TFH) cells. During SLE pathogenesis, basophils accumulate in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms that remain to be defined. Here, we provide evidence for a direct functional relationship between TFH cells and basophils during lupus pathogenesis, both in humans and mice. PD-L1 upregulation on basophils and IL-4 production are associated with TFH and TFH2 cell expansions and with disease activity. Pathogenic TFH cell accumulation, maintenance, and function in SLO were dependent on PD-L1 and IL-4 in basophils, which induced a transcriptional program allowing TFH2 cell differentiation and function. Our study establishes a direct mechanistic link between basophils and TFH cells in SLE that promotes autoantibody production and lupus nephritis.
publishDate 2024
dc.date.none.fl_str_mv 2
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/310540
https://dx.doi.org/urn:doi:10.1038/s41467-024-47691-w
url https://ddd.uab.cat/record/310540
https://dx.doi.org/urn:doi:10.1038/s41467-024-47691-w
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-101105-B-I00
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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