Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation

Ríos, Israel; Herrero, Cristina; Torres-Torresano, Mónica; López-Navarro, Baltasar; Schiaffino, María Teresa; Díaz Crespo, Francisco; Nieto-Valle, Alicia; Samaniego, Rafael; Sierra-Palomares, Yolanda; Oliver, Eduardo; Revuelta-Salgado, Fernando; García-Luján, Ricardo; Sánchez-Mateos, Paloma; Delgado, Rafael; Puig-Kröger, Amaya; Corbí, Angel L.

Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation

Monocyte-derived macrophages recruited into inflamed tissues can acquire an array of functional states depending on the extracellular environment. Since the anti-inflammatory/pro-fibrotic macrophage profile is determined by MAFB, whose activity/protein levels are regulated by GSK3, we addressed the...

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Detalles Bibliográficos
Autores:	Ríos, Israel, Herrero, Cristina, Torres-Torresano, Mónica, López-Navarro, Baltasar, Schiaffino, María Teresa, Díaz Crespo, Francisco, Nieto-Valle, Alicia, Samaniego, Rafael, Sierra-Palomares, Yolanda, Oliver, Eduardo, Revuelta-Salgado, Fernando, García-Luján, Ricardo, Sánchez-Mateos, Paloma, Delgado, Rafael, Puig-Kröger, Amaya, Corbí, Angel L.
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2025
País:	España
Institución:	Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:	DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:	oai:digital.csic.es:10261/390202
Acceso en línea:	http://hdl.handle.net/10261/390202
Access Level:	acceso abierto
Palabra clave:	GSK3 human immunology inflammation macrophage reprogramming macrophages

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network_acronym_str	ES
network_name_str	España
repository_id_str
dc.title.none.fl_str_mv	Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation
title	Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation
spellingShingle	Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation Ríos, Israel GSK3 human immunology inflammation macrophage reprogramming macrophages
title_short	Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation
title_full	Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation
title_fullStr	Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation
title_full_unstemmed	Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation
title_sort	Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation
dc.creator.none.fl_str_mv	Ríos, Israel Herrero, Cristina Torres-Torresano, Mónica López-Navarro, Baltasar Schiaffino, María Teresa Díaz Crespo, Francisco Nieto-Valle, Alicia Samaniego, Rafael Sierra-Palomares, Yolanda Oliver, Eduardo Revuelta-Salgado, Fernando García-Luján, Ricardo Sánchez-Mateos, Paloma Delgado, Rafael Puig-Kröger, Amaya Corbí, Angel L.
author	Ríos, Israel
author_facet	Ríos, Israel Herrero, Cristina Torres-Torresano, Mónica López-Navarro, Baltasar Schiaffino, María Teresa Díaz Crespo, Francisco Nieto-Valle, Alicia Samaniego, Rafael Sierra-Palomares, Yolanda Oliver, Eduardo Revuelta-Salgado, Fernando García-Luján, Ricardo Sánchez-Mateos, Paloma Delgado, Rafael Puig-Kröger, Amaya Corbí, Angel L.
author_role	author
author2	Herrero, Cristina Torres-Torresano, Mónica López-Navarro, Baltasar Schiaffino, María Teresa Díaz Crespo, Francisco Nieto-Valle, Alicia Samaniego, Rafael Sierra-Palomares, Yolanda Oliver, Eduardo Revuelta-Salgado, Fernando García-Luján, Ricardo Sánchez-Mateos, Paloma Delgado, Rafael Puig-Kröger, Amaya Corbí, Angel L.
author2_role	author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Comunidad de Madrid Instituto de Salud Carlos III Agencia Estatal de Investigación (España) Ministerio de Ciencia, Innovación y Universidades (España) Red de Enfermedades Inflamatorias (España) European Commission CSIC - Plataforma Temática Interdisciplinar del CSIC Salud Global (PTI Salud Global) Oliver, Eduardo [0000-0001-9340-882X] Corbí, Angel L. [0000-0003-1980-5733] Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv	GSK3 human immunology inflammation macrophage reprogramming macrophages
topic	GSK3 human immunology inflammation macrophage reprogramming macrophages
description	Monocyte-derived macrophages recruited into inflamed tissues can acquire an array of functional states depending on the extracellular environment. Since the anti-inflammatory/pro-fibrotic macrophage profile is determined by MAFB, whose activity/protein levels are regulated by GSK3, we addressed the macrophage reprogramming potential of GSK3 modulation. GM-CSF-dependent (GM-MØ) and M-CSF-dependent monocyte-derived macrophages (M-MØ) exhibited distinct levels of inactive GSK3, and inhibiting GSK3 in GM-MØ led to the acquisition of transcriptional, phenotypic, and functional properties characteristic of M-MØ (enhanced expression of IL-10 and monocyte-recruiting factors, and higher efferocytosis). These reprogramming effects were also observed upon GSK3α/β knockdown and through GSK3 inhibition in ex vivo isolated human alveolar macrophages (AMØ). Notably, GSK3 downmodulation potentiated the transcriptional signature of interstitial macrophages (IMØ) while suppressing the AMØ-specific gene profile. Indeed, heightened levels of inactive GSK3 and MAFB-dependent proteins were observed in severe COVID-19 patients' lung macrophages, highlighting the GSK3-MAFB axis as a therapeutic target for macrophage reprogramming.
publishDate	2025
dc.date.none.fl_str_mv	2025 2025 2025
dc.type.none.fl_str_mv	info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10261/390202
url	http://hdl.handle.net/10261/390202
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	#PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114323RB-I00 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-123167OB-I00 The dataset supporting the conclusions of this article is available in the Gene Expression Omnibus repository (http://www.ncbi.nlm.nih.gov/geo/) under accession GSE256538 (monocytes exposed to CHIR99021 or DMSO), GSE256208 (GM-MØ exposed to CHIR99021 or DMSO), GSE262463 (alveolar macrophages exposed to CHIR99021 or DMSO), and GSE266236 (GM-MØ after GSK3α/β knockdown). https://doi.org/10.7554/eLife.102659 Sí
dc.rights.none.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	eLife Sciences Publications
publisher.none.fl_str_mv	eLife Sciences Publications
dc.source.none.fl_str_mv	reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str	Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str	DIGITAL.CSIC. Repositorio Institucional del CSIC
collection	DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
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spelling	Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulationRíos, IsraelHerrero, CristinaTorres-Torresano, MónicaLópez-Navarro, BaltasarSchiaffino, María TeresaDíaz Crespo, FranciscoNieto-Valle, AliciaSamaniego, RafaelSierra-Palomares, YolandaOliver, EduardoRevuelta-Salgado, FernandoGarcía-Luján, RicardoSánchez-Mateos, PalomaDelgado, RafaelPuig-Kröger, AmayaCorbí, Angel L.GSK3humanimmunologyinflammationmacrophage reprogrammingmacrophagesMonocyte-derived macrophages recruited into inflamed tissues can acquire an array of functional states depending on the extracellular environment. Since the anti-inflammatory/pro-fibrotic macrophage profile is determined by MAFB, whose activity/protein levels are regulated by GSK3, we addressed the macrophage reprogramming potential of GSK3 modulation. GM-CSF-dependent (GM-MØ) and M-CSF-dependent monocyte-derived macrophages (M-MØ) exhibited distinct levels of inactive GSK3, and inhibiting GSK3 in GM-MØ led to the acquisition of transcriptional, phenotypic, and functional properties characteristic of M-MØ (enhanced expression of IL-10 and monocyte-recruiting factors, and higher efferocytosis). These reprogramming effects were also observed upon GSK3α/β knockdown and through GSK3 inhibition in ex vivo isolated human alveolar macrophages (AMØ). Notably, GSK3 downmodulation potentiated the transcriptional signature of interstitial macrophages (IMØ) while suppressing the AMØ-specific gene profile. Indeed, heightened levels of inactive GSK3 and MAFB-dependent proteins were observed in severe COVID-19 patients' lung macrophages, highlighting the GSK3-MAFB axis as a therapeutic target for macrophage reprogramming.This work was supported by grant PID2020- 114323RB- I00 from Ministerio de Ciencia e Innovación to ALC, Dirección General de Innovación e Investigación Tecnológica de la Comunidad de Madrid (RETARACOVID, P2022/BMD- 7274) to ALC, APK, PS- M, and RD, Instituto de Salud Carlos III (Grant PI23/00224 to APK, Grant PI21/00989 to RD), Red de Enfermedades Inflamatorias (RICORSRD21/0002/0034) from Instituto de Salud Carlos III and cofinanced by the Euopean Regional Devel-opment Fund 'A way to achieve Europe' (ERDF) and PRTR to APK, and PID2021- 123167OB- I00 from Ministerio de Ciencia, Innovación y Universidades and CSIC Talent Attraction program (20222AT010) to EO. This research work was also funded by the European Commission – NextGenerationEU (Regu-lation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global). AN- V was funded by YEI program contract from Comunidad de Madrid (PEJ- 2021- AI/BMD- 23327). IR was funded by a Formación de Personal Investigador predoctoral fellowship from Ministerio de Ciencia e Innovación (Grant PRE2021- 097080). Figures were created with Biorender.com.Peer reviewedeLife Sciences PublicationsComunidad de MadridInstituto de Salud Carlos IIIAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Red de Enfermedades Inflamatorias (España)European CommissionCSIC - Plataforma Temática Interdisciplinar del CSIC Salud Global (PTI Salud Global)Oliver, Eduardo [0000-0001-9340-882X]Corbí, Angel L. [0000-0003-1980-5733]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/390202reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114323RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-123167OB-I00The dataset supporting the conclusions of this article is available in the Gene Expression Omnibus repository (http://www.ncbi.nlm.nih.gov/geo/) under accession GSE256538 (monocytes exposed to CHIR99021 or DMSO), GSE256208 (GM-MØ exposed to CHIR99021 or DMSO), GSE262463 (alveolar macrophages exposed to CHIR99021 or DMSO), and GSE266236 (GM-MØ after GSK3α/β knockdown).https://doi.org/10.7554/eLife.102659Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3902022026-05-22T06:33:51Z
score	15,811543

Reprogramming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation

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