Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage

Perugorria, M.J. (María J.)|||/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9; Esparza-Baquer, A. (Aitor)|||/items/438e0a22-4750-4f6d-b262-4b64c8e20594; Oakley, F. (Fiona)|||/items/9034ea65-4a72-40af-aba1-be694ebf5341; Labiano, I. (Ibone)|||/items/184c5ecc-80d3-4326-afc1-93295ec4ba66; Korosec, A. (Ana)|||/items/9c07d9f0-6022-4837-a8b6-ab700cf3a5c8; Jais, A. (Alexander)|||/items/78698089-a126-4a26-970a-e26ea1203740; Mann, J. (Jelena)|||/items/62541d21-a7b1-4e3b-a579-eb63b7469880; Tiniakos, D. (Dina)|||/items/c90fe176-7a1b-43da-a68d-06214bbc08a5; Santos-Laso, A. (Alvaro)|||/items/b8ad1b5e-7690-465e-9e75-3f3a9f46c9ea; Arbelaiz, A. (Ander)|||/items/4f26aa12-14f5-4353-9c23-5ae1c3b89cad; Gawish, R. (Riem)|||/items/057f910d-b595-4d9e-bff8-e05e60d8ec39; Sampedro, A. (Ana)|||/items/321381d5-15ba-4d73-b82e-fbeaa4d9cb39; Fontanellas-Romá, A. (Antonio)|||/items/4ca7871d-480e-4841-b383-6a0da85f3a81; Hijona, E. (Elizabeth)|||/items/0c0fdba6-e27f-4a18-a09c-a3687ace1931; Jimenez-Agüero, R. (Raul)|||/items/45004528-912d-4c2a-8ba9-29dce7316193; Esterbauer, H. (Harald)|||/items/16985d98-7123-4530-ad54-384506baccc7; Stoiber, D. (Dagmar)|||/items/f106486e-51bf-4056-a167-64049ea83be8; Bujanda, L. (Luis)|||/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85; Banales, J.M. (Jesús M.)|||/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5; Knapp, S. (Sylvia)|||/items/65c7c935-a3f5-44bd-8c3f-f83a495ab24e; Sharif, O. (Omar)|||/items/4f48f1c9-5140-4309-85a9-da4bc294a684; Mann, D.A. (Derek A.)|||/items/37f08a32-b9eb-45ef-ada4-de51fc1eb4ee

Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage

Objective: Liver injury impacts hepatic inflammation in part via Toll-like receptor (TLR) signalling. Triggering receptor expressed on myeloid cells 2 (TREM-2) modulates TLR4-mediated inflammation in bone marrow (BM)-derived macrophages but its function in liver injury is unknown. Here we hypothesis...

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Detalles Bibliográficos
Autores:	Perugorria, M.J. (María J.)\|\|\|/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9, Esparza-Baquer, A. (Aitor)\|\|\|/items/438e0a22-4750-4f6d-b262-4b64c8e20594, Oakley, F. (Fiona)\|\|\|/items/9034ea65-4a72-40af-aba1-be694ebf5341, Labiano, I. (Ibone)\|\|\|/items/184c5ecc-80d3-4326-afc1-93295ec4ba66, Korosec, A. (Ana)\|\|\|/items/9c07d9f0-6022-4837-a8b6-ab700cf3a5c8, Jais, A. (Alexander)\|\|\|/items/78698089-a126-4a26-970a-e26ea1203740, Mann, J. (Jelena)\|\|\|/items/62541d21-a7b1-4e3b-a579-eb63b7469880, Tiniakos, D. (Dina)\|\|\|/items/c90fe176-7a1b-43da-a68d-06214bbc08a5, Santos-Laso, A. (Alvaro)\|\|\|/items/b8ad1b5e-7690-465e-9e75-3f3a9f46c9ea, Arbelaiz, A. (Ander)\|\|\|/items/4f26aa12-14f5-4353-9c23-5ae1c3b89cad, Gawish, R. (Riem)\|\|\|/items/057f910d-b595-4d9e-bff8-e05e60d8ec39, Sampedro, A. (Ana)\|\|\|/items/321381d5-15ba-4d73-b82e-fbeaa4d9cb39, Fontanellas-Romá, A. (Antonio)\|\|\|/items/4ca7871d-480e-4841-b383-6a0da85f3a81, Hijona, E. (Elizabeth)\|\|\|/items/0c0fdba6-e27f-4a18-a09c-a3687ace1931, Jimenez-Agüero, R. (Raul)\|\|\|/items/45004528-912d-4c2a-8ba9-29dce7316193, Esterbauer, H. (Harald)\|\|\|/items/16985d98-7123-4530-ad54-384506baccc7, Stoiber, D. (Dagmar)\|\|\|/items/f106486e-51bf-4056-a167-64049ea83be8, Bujanda, L. (Luis)\|\|\|/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85, Banales, J.M. (Jesús M.)\|\|\|/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5, Knapp, S. (Sylvia)\|\|\|/items/65c7c935-a3f5-44bd-8c3f-f83a495ab24e, Sharif, O. (Omar)\|\|\|/items/4f48f1c9-5140-4309-85a9-da4bc294a684, Mann, D.A. (Derek A.)\|\|\|/items/37f08a32-b9eb-45ef-ada4-de51fc1eb4ee
Tipo de recurso:	artículo
Fecha de publicación:	2019
País:	España
Institución:	Universidad de Navarra
Repositorio:	Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:	inglés
OAI Identifier:	oai:dadun.unav.edu:10171/63510
Acceso en línea:	https://hdl.handle.net/10171/63510
Access Level:	acceso abierto
Palabra clave:	Acute liver failure Chronic liver disease Hepatic stellate cell Immune-mediated liver damage Inflammation

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spelling	Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damagePerugorria, M.J. (María J.)\|\|\|/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9Esparza-Baquer, A. (Aitor)\|\|\|/items/438e0a22-4750-4f6d-b262-4b64c8e20594Oakley, F. (Fiona)\|\|\|/items/9034ea65-4a72-40af-aba1-be694ebf5341Labiano, I. (Ibone)\|\|\|/items/184c5ecc-80d3-4326-afc1-93295ec4ba66Korosec, A. (Ana)\|\|\|/items/9c07d9f0-6022-4837-a8b6-ab700cf3a5c8Jais, A. (Alexander)\|\|\|/items/78698089-a126-4a26-970a-e26ea1203740Mann, J. (Jelena)\|\|\|/items/62541d21-a7b1-4e3b-a579-eb63b7469880Tiniakos, D. (Dina)\|\|\|/items/c90fe176-7a1b-43da-a68d-06214bbc08a5Santos-Laso, A. (Alvaro)\|\|\|/items/b8ad1b5e-7690-465e-9e75-3f3a9f46c9eaArbelaiz, A. (Ander)\|\|\|/items/4f26aa12-14f5-4353-9c23-5ae1c3b89cadGawish, R. (Riem)\|\|\|/items/057f910d-b595-4d9e-bff8-e05e60d8ec39Sampedro, A. (Ana)\|\|\|/items/321381d5-15ba-4d73-b82e-fbeaa4d9cb39Fontanellas-Romá, A. (Antonio)\|\|\|/items/4ca7871d-480e-4841-b383-6a0da85f3a81Hijona, E. (Elizabeth)\|\|\|/items/0c0fdba6-e27f-4a18-a09c-a3687ace1931Jimenez-Agüero, R. (Raul)\|\|\|/items/45004528-912d-4c2a-8ba9-29dce7316193Esterbauer, H. (Harald)\|\|\|/items/16985d98-7123-4530-ad54-384506baccc7Stoiber, D. (Dagmar)\|\|\|/items/f106486e-51bf-4056-a167-64049ea83be8Bujanda, L. (Luis)\|\|\|/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85Banales, J.M. (Jesús M.)\|\|\|/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5Knapp, S. (Sylvia)\|\|\|/items/65c7c935-a3f5-44bd-8c3f-f83a495ab24eSharif, O. (Omar)\|\|\|/items/4f48f1c9-5140-4309-85a9-da4bc294a684Mann, D.A. (Derek A.)\|\|\|/items/37f08a32-b9eb-45ef-ada4-de51fc1eb4eeAcute liver failureChronic liver diseaseHepatic stellate cellImmune-mediated liver damageInflammationObjective: Liver injury impacts hepatic inflammation in part via Toll-like receptor (TLR) signalling. Triggering receptor expressed on myeloid cells 2 (TREM-2) modulates TLR4-mediated inflammation in bone marrow (BM)-derived macrophages but its function in liver injury is unknown. Here we hypothesised that the anti-inflammatory effects of TREM-2 on TLR signalling may limit hepatic injury. Design: TREM-2 expression was analysed in livers of humans with various forms of liver injury compared with control individuals. Acute and chronic liver injury models were performed in wild type and Trem-2-/- mice. Primary liver cells from both genotypes of mice were isolated for in vitro experiments. Results: TREM-2 was expressed on non-parenchymal hepatic cells and induced during liver injury in mice and man. Mice lacking TREM-2 exhibited heightened liver damage and inflammation during acute and repetitive carbon tetrachloride and acetaminophen (APAP) intoxication, the latter of which TREM-2 deficiency was remarkably associated with worsened survival. Liver damage in Trem-2-/- mice following chronic injury and APAP challenge was associated with elevated hepatic lipid peroxidation and macrophage content. BM transplantation experiments and cellular reactive oxygen species assays revealed effects of TREM-2 in the context of chronic injury depended on both immune and resident TREM-2 expression. Consistent with effects of TREM-2 on inflammation-associated injury, primary hepatic macrophages and hepatic stellate cells lacking TREM-2 exhibited augmented TLR4-driven proinflammatory responses. Conclusion: Our data indicate that by acting as a natural brake on inflammation during hepatocellular injury, TREM-2 is a critical regulator of diverse types of hepatotoxic injury.BMJDadun. Depósito Académico Digital Universidad de Navarra20222022-05-2420192019-01-0120192019-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/63510reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/635102026-06-21T12:47:57Z
dc.title.none.fl_str_mv	Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage
title	Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage
spellingShingle	Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage Perugorria, M.J. (María J.)\|\|\|/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9 Acute liver failure Chronic liver disease Hepatic stellate cell Immune-mediated liver damage Inflammation
title_short	Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage
title_full	Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage
title_fullStr	Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage
title_full_unstemmed	Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage
title_sort	Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage
dc.creator.none.fl_str_mv	Perugorria, M.J. (María J.)\|\|\|/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9 Esparza-Baquer, A. (Aitor)\|\|\|/items/438e0a22-4750-4f6d-b262-4b64c8e20594 Oakley, F. (Fiona)\|\|\|/items/9034ea65-4a72-40af-aba1-be694ebf5341 Labiano, I. (Ibone)\|\|\|/items/184c5ecc-80d3-4326-afc1-93295ec4ba66 Korosec, A. (Ana)\|\|\|/items/9c07d9f0-6022-4837-a8b6-ab700cf3a5c8 Jais, A. (Alexander)\|\|\|/items/78698089-a126-4a26-970a-e26ea1203740 Mann, J. (Jelena)\|\|\|/items/62541d21-a7b1-4e3b-a579-eb63b7469880 Tiniakos, D. (Dina)\|\|\|/items/c90fe176-7a1b-43da-a68d-06214bbc08a5 Santos-Laso, A. (Alvaro)\|\|\|/items/b8ad1b5e-7690-465e-9e75-3f3a9f46c9ea Arbelaiz, A. (Ander)\|\|\|/items/4f26aa12-14f5-4353-9c23-5ae1c3b89cad Gawish, R. (Riem)\|\|\|/items/057f910d-b595-4d9e-bff8-e05e60d8ec39 Sampedro, A. (Ana)\|\|\|/items/321381d5-15ba-4d73-b82e-fbeaa4d9cb39 Fontanellas-Romá, A. (Antonio)\|\|\|/items/4ca7871d-480e-4841-b383-6a0da85f3a81 Hijona, E. (Elizabeth)\|\|\|/items/0c0fdba6-e27f-4a18-a09c-a3687ace1931 Jimenez-Agüero, R. (Raul)\|\|\|/items/45004528-912d-4c2a-8ba9-29dce7316193 Esterbauer, H. (Harald)\|\|\|/items/16985d98-7123-4530-ad54-384506baccc7 Stoiber, D. (Dagmar)\|\|\|/items/f106486e-51bf-4056-a167-64049ea83be8 Bujanda, L. (Luis)\|\|\|/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85 Banales, J.M. (Jesús M.)\|\|\|/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5 Knapp, S. (Sylvia)\|\|\|/items/65c7c935-a3f5-44bd-8c3f-f83a495ab24e Sharif, O. (Omar)\|\|\|/items/4f48f1c9-5140-4309-85a9-da4bc294a684 Mann, D.A. (Derek A.)\|\|\|/items/37f08a32-b9eb-45ef-ada4-de51fc1eb4ee
author	Perugorria, M.J. (María J.)\|\|\|/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9
author_facet	Perugorria, M.J. (María J.)\|\|\|/items/bc5acab9-2480-4b1a-a8b7-72354639c5d9 Esparza-Baquer, A. (Aitor)\|\|\|/items/438e0a22-4750-4f6d-b262-4b64c8e20594 Oakley, F. (Fiona)\|\|\|/items/9034ea65-4a72-40af-aba1-be694ebf5341 Labiano, I. (Ibone)\|\|\|/items/184c5ecc-80d3-4326-afc1-93295ec4ba66 Korosec, A. (Ana)\|\|\|/items/9c07d9f0-6022-4837-a8b6-ab700cf3a5c8 Jais, A. (Alexander)\|\|\|/items/78698089-a126-4a26-970a-e26ea1203740 Mann, J. (Jelena)\|\|\|/items/62541d21-a7b1-4e3b-a579-eb63b7469880 Tiniakos, D. (Dina)\|\|\|/items/c90fe176-7a1b-43da-a68d-06214bbc08a5 Santos-Laso, A. (Alvaro)\|\|\|/items/b8ad1b5e-7690-465e-9e75-3f3a9f46c9ea Arbelaiz, A. (Ander)\|\|\|/items/4f26aa12-14f5-4353-9c23-5ae1c3b89cad Gawish, R. (Riem)\|\|\|/items/057f910d-b595-4d9e-bff8-e05e60d8ec39 Sampedro, A. (Ana)\|\|\|/items/321381d5-15ba-4d73-b82e-fbeaa4d9cb39 Fontanellas-Romá, A. (Antonio)\|\|\|/items/4ca7871d-480e-4841-b383-6a0da85f3a81 Hijona, E. (Elizabeth)\|\|\|/items/0c0fdba6-e27f-4a18-a09c-a3687ace1931 Jimenez-Agüero, R. (Raul)\|\|\|/items/45004528-912d-4c2a-8ba9-29dce7316193 Esterbauer, H. (Harald)\|\|\|/items/16985d98-7123-4530-ad54-384506baccc7 Stoiber, D. (Dagmar)\|\|\|/items/f106486e-51bf-4056-a167-64049ea83be8 Bujanda, L. (Luis)\|\|\|/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85 Banales, J.M. (Jesús M.)\|\|\|/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5 Knapp, S. (Sylvia)\|\|\|/items/65c7c935-a3f5-44bd-8c3f-f83a495ab24e Sharif, O. (Omar)\|\|\|/items/4f48f1c9-5140-4309-85a9-da4bc294a684 Mann, D.A. (Derek A.)\|\|\|/items/37f08a32-b9eb-45ef-ada4-de51fc1eb4ee
author_role	author
author2	Esparza-Baquer, A. (Aitor)\|\|\|/items/438e0a22-4750-4f6d-b262-4b64c8e20594 Oakley, F. (Fiona)\|\|\|/items/9034ea65-4a72-40af-aba1-be694ebf5341 Labiano, I. (Ibone)\|\|\|/items/184c5ecc-80d3-4326-afc1-93295ec4ba66 Korosec, A. (Ana)\|\|\|/items/9c07d9f0-6022-4837-a8b6-ab700cf3a5c8 Jais, A. (Alexander)\|\|\|/items/78698089-a126-4a26-970a-e26ea1203740 Mann, J. (Jelena)\|\|\|/items/62541d21-a7b1-4e3b-a579-eb63b7469880 Tiniakos, D. (Dina)\|\|\|/items/c90fe176-7a1b-43da-a68d-06214bbc08a5 Santos-Laso, A. (Alvaro)\|\|\|/items/b8ad1b5e-7690-465e-9e75-3f3a9f46c9ea Arbelaiz, A. (Ander)\|\|\|/items/4f26aa12-14f5-4353-9c23-5ae1c3b89cad Gawish, R. (Riem)\|\|\|/items/057f910d-b595-4d9e-bff8-e05e60d8ec39 Sampedro, A. (Ana)\|\|\|/items/321381d5-15ba-4d73-b82e-fbeaa4d9cb39 Fontanellas-Romá, A. (Antonio)\|\|\|/items/4ca7871d-480e-4841-b383-6a0da85f3a81 Hijona, E. (Elizabeth)\|\|\|/items/0c0fdba6-e27f-4a18-a09c-a3687ace1931 Jimenez-Agüero, R. (Raul)\|\|\|/items/45004528-912d-4c2a-8ba9-29dce7316193 Esterbauer, H. (Harald)\|\|\|/items/16985d98-7123-4530-ad54-384506baccc7 Stoiber, D. (Dagmar)\|\|\|/items/f106486e-51bf-4056-a167-64049ea83be8 Bujanda, L. (Luis)\|\|\|/items/bed21b6f-08f6-4f90-ad12-a31c1ee87d85 Banales, J.M. (Jesús M.)\|\|\|/items/0c1309ae-e4e4-4e85-b2f1-567a388889d5 Knapp, S. (Sylvia)\|\|\|/items/65c7c935-a3f5-44bd-8c3f-f83a495ab24e Sharif, O. (Omar)\|\|\|/items/4f48f1c9-5140-4309-85a9-da4bc294a684 Mann, D.A. (Derek A.)\|\|\|/items/37f08a32-b9eb-45ef-ada4-de51fc1eb4ee
author2_role	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	Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv	Acute liver failure Chronic liver disease Hepatic stellate cell Immune-mediated liver damage Inflammation
topic	Acute liver failure Chronic liver disease Hepatic stellate cell Immune-mediated liver damage Inflammation
description	Objective: Liver injury impacts hepatic inflammation in part via Toll-like receptor (TLR) signalling. Triggering receptor expressed on myeloid cells 2 (TREM-2) modulates TLR4-mediated inflammation in bone marrow (BM)-derived macrophages but its function in liver injury is unknown. Here we hypothesised that the anti-inflammatory effects of TREM-2 on TLR signalling may limit hepatic injury. Design: TREM-2 expression was analysed in livers of humans with various forms of liver injury compared with control individuals. Acute and chronic liver injury models were performed in wild type and Trem-2-/- mice. Primary liver cells from both genotypes of mice were isolated for in vitro experiments. Results: TREM-2 was expressed on non-parenchymal hepatic cells and induced during liver injury in mice and man. Mice lacking TREM-2 exhibited heightened liver damage and inflammation during acute and repetitive carbon tetrachloride and acetaminophen (APAP) intoxication, the latter of which TREM-2 deficiency was remarkably associated with worsened survival. Liver damage in Trem-2-/- mice following chronic injury and APAP challenge was associated with elevated hepatic lipid peroxidation and macrophage content. BM transplantation experiments and cellular reactive oxygen species assays revealed effects of TREM-2 in the context of chronic injury depended on both immune and resident TREM-2 expression. Consistent with effects of TREM-2 on inflammation-associated injury, primary hepatic macrophages and hepatic stellate cells lacking TREM-2 exhibited augmented TLR4-driven proinflammatory responses. Conclusion: Our data indicate that by acting as a natural brake on inflammation during hepatocellular injury, TREM-2 is a critical regulator of diverse types of hepatotoxic injury.
publishDate	2019
dc.date.none.fl_str_mv	2019 2019-01-01 2019 2019-01-01 2022 2022-05-24
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/10171/63510
url	https://hdl.handle.net/10171/63510
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2
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
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	BMJ
publisher.none.fl_str_mv	BMJ
dc.source.none.fl_str_mv	reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra
instname_str	Universidad de Navarra
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Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage

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