Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage

Detalhes bibliográficos
Autor(a) principal: Coelho, Inês
Data de Publicação: 2021
Outros Autores: Duarte, Nádia, Barros, André, Macedo, Maria Paula, Penha-Gonçalves, Carlos
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/113692
Resumo: This work was developed with the support of the research infrastructure Congento, project LISBOA-01-0145-FEDER022170, co-financed by Lisboa Regional Operational Programme (Lisboa 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and FCT – “Fundação para a Ciência e a Tecnologia” (Portugal). This work was partially supported by ONEIDA project (LISBOA-01-0145-FEDER016417) co-funded by FEEI – “Fundos Europeus Estruturais e de Investimento” from “Programa Operacional Regional Lisboa 2020” and by national funds from FCT through grants PTDC/ BIM-MET/2115/2014, PTDC/BIM-MET/4265/2014 and iNOVA4Health (UID/Multi/04462/2013). IC was supported by a FCT fellowship PD/BD/105997/2014
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spelling Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damageacetaminophen (paracetamol)carbon tetrachloride 4endothelial cellsinflammationmacrophagestissue repair and organ regenerationtriggering receptor expressed on myeloid cells 2Immunology and AllergyImmunologyThis work was developed with the support of the research infrastructure Congento, project LISBOA-01-0145-FEDER022170, co-financed by Lisboa Regional Operational Programme (Lisboa 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and FCT – “Fundação para a Ciência e a Tecnologia” (Portugal). This work was partially supported by ONEIDA project (LISBOA-01-0145-FEDER016417) co-funded by FEEI – “Fundos Europeus Estruturais e de Investimento” from “Programa Operacional Regional Lisboa 2020” and by national funds from FCT through grants PTDC/ BIM-MET/2115/2014, PTDC/BIM-MET/4265/2014 and iNOVA4Health (UID/Multi/04462/2013). IC was supported by a FCT fellowship PD/BD/105997/2014Macrophages are pivotal in mounting liver inflammatory and tissue repair responses upon hepatic injury, showing remarkable functional plasticity. The molecular mechanisms determining macrophage transition from inflammatory to restorative phenotypes in the damaged liver remain unclear. Using mouse models of acute (APAP) and chronic (CCl4) drug-induced hepatotoxic injury we show that the immune receptor Trem-2 controls phenotypic shifts of liver macrophages and impacts endothelial cell differentiation during tissue recovery. Trem-2 gene ablation led to a delayed re-population of Kupffer cells correlating with deterred resolution of hepatic damage following acute and chronic injury. During tissue recovery, we found that macrophages transitioning to Kupffer cells expressed high levels of Trem-2. Acquisition of the transition phenotype was associated with a unique transcriptomic profile denoting strong responsiveness to oxidative stress and downmodulation of the pro-inflammatory phenotype, which was not observed in absence of Trem-2. During tissue recovery, lack of Trem-2 favored accumulation of a liver-damage associated endothelial cell population (LDECs), whose transcriptional program was compatible with endothelial de-differentiation. Accordingly, LDECs precursor potential is supported by the downregulation of surface endothelial cell markers and by striking in vitro morphological changes towards typical endothelial cells. In conclusion, we found that the dynamics of liver macrophages in response to liver injury are critically controlled by Trem-2 and this regulation is interlinked with the de-differentiation of endothelial cells and heightened liver pathology. We propose that Trem-2 promotes the transition from pro-inflammatory to tissue repair phase by driving the acquisition of restorative properties in phagocytic macrophages.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNCoelho, InêsDuarte, NádiaBarros, AndréMacedo, Maria PaulaPenha-Gonçalves, Carlos2021-03-10T23:55:20Z2021-02-082021-02-08T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/113692eng1664-3224PURE: 28404624https://doi.org/10.3389/fimmu.2020.616044info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:56:35Zoai:run.unl.pt:10362/113692Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:42:21.688758Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage
title Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage
spellingShingle Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage
Coelho, Inês
acetaminophen (paracetamol)
carbon tetrachloride 4
endothelial cells
inflammation
macrophages
tissue repair and organ regeneration
triggering receptor expressed on myeloid cells 2
Immunology and Allergy
Immunology
title_short Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage
title_full Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage
title_fullStr Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage
title_full_unstemmed Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage
title_sort Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage
author Coelho, Inês
author_facet Coelho, Inês
Duarte, Nádia
Barros, André
Macedo, Maria Paula
Penha-Gonçalves, Carlos
author_role author
author2 Duarte, Nádia
Barros, André
Macedo, Maria Paula
Penha-Gonçalves, Carlos
author2_role author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
RUN
dc.contributor.author.fl_str_mv Coelho, Inês
Duarte, Nádia
Barros, André
Macedo, Maria Paula
Penha-Gonçalves, Carlos
dc.subject.por.fl_str_mv acetaminophen (paracetamol)
carbon tetrachloride 4
endothelial cells
inflammation
macrophages
tissue repair and organ regeneration
triggering receptor expressed on myeloid cells 2
Immunology and Allergy
Immunology
topic acetaminophen (paracetamol)
carbon tetrachloride 4
endothelial cells
inflammation
macrophages
tissue repair and organ regeneration
triggering receptor expressed on myeloid cells 2
Immunology and Allergy
Immunology
description This work was developed with the support of the research infrastructure Congento, project LISBOA-01-0145-FEDER022170, co-financed by Lisboa Regional Operational Programme (Lisboa 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and FCT – “Fundação para a Ciência e a Tecnologia” (Portugal). This work was partially supported by ONEIDA project (LISBOA-01-0145-FEDER016417) co-funded by FEEI – “Fundos Europeus Estruturais e de Investimento” from “Programa Operacional Regional Lisboa 2020” and by national funds from FCT through grants PTDC/ BIM-MET/2115/2014, PTDC/BIM-MET/4265/2014 and iNOVA4Health (UID/Multi/04462/2013). IC was supported by a FCT fellowship PD/BD/105997/2014
publishDate 2021
dc.date.none.fl_str_mv 2021-03-10T23:55:20Z
2021-02-08
2021-02-08T00:00:00Z
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/10362/113692
url http://hdl.handle.net/10362/113692
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1664-3224
PURE: 28404624
https://doi.org/10.3389/fimmu.2020.616044
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:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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