Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury

Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Manuel Flores Molina [verfasserIn] Mohamed N. Abdelnabi [verfasserIn] Sabrina Mazouz [verfasserIn] Deborah Villafranca-Baughman [verfasserIn] Vincent Quoc-Huy Trinh [verfasserIn] Shafi Muhammad [verfasserIn] Nathalie Bédard [verfasserIn] David Osorio Laverde [verfasserIn] Ghada S. Hassan [verfasserIn] Adriana Di Polo [verfasserIn] Naglaa H. Shoukry [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 13(2022)
Übergeordnetes Werk:	volume:13 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2022.994480

Katalog-ID:	DOAJ022188606

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allfields	10.3389/fimmu.2022.994480 doi (DE-627)DOAJ022188606 (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 DE-627 ger DE-627 rakwb eng RC581-607 Manuel Flores Molina verfasserin aut Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy Manuel Flores Molina verfasserin aut Mohamed N. Abdelnabi verfasserin aut Mohamed N. Abdelnabi verfasserin aut Sabrina Mazouz verfasserin aut Sabrina Mazouz verfasserin aut Deborah Villafranca-Baughman verfasserin aut Deborah Villafranca-Baughman verfasserin aut Vincent Quoc-Huy Trinh verfasserin aut Shafi Muhammad verfasserin aut Shafi Muhammad verfasserin aut Nathalie Bédard verfasserin aut David Osorio Laverde verfasserin aut Ghada S. Hassan verfasserin aut Adriana Di Polo verfasserin aut Adriana Di Polo verfasserin aut Naglaa H. Shoukry verfasserin aut Naglaa H. Shoukry verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.994480 kostenfrei https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
spelling	10.3389/fimmu.2022.994480 doi (DE-627)DOAJ022188606 (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 DE-627 ger DE-627 rakwb eng RC581-607 Manuel Flores Molina verfasserin aut Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy Manuel Flores Molina verfasserin aut Mohamed N. Abdelnabi verfasserin aut Mohamed N. Abdelnabi verfasserin aut Sabrina Mazouz verfasserin aut Sabrina Mazouz verfasserin aut Deborah Villafranca-Baughman verfasserin aut Deborah Villafranca-Baughman verfasserin aut Vincent Quoc-Huy Trinh verfasserin aut Shafi Muhammad verfasserin aut Shafi Muhammad verfasserin aut Nathalie Bédard verfasserin aut David Osorio Laverde verfasserin aut Ghada S. Hassan verfasserin aut Adriana Di Polo verfasserin aut Adriana Di Polo verfasserin aut Naglaa H. Shoukry verfasserin aut Naglaa H. Shoukry verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.994480 kostenfrei https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfields_unstemmed	10.3389/fimmu.2022.994480 doi (DE-627)DOAJ022188606 (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 DE-627 ger DE-627 rakwb eng RC581-607 Manuel Flores Molina verfasserin aut Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy Manuel Flores Molina verfasserin aut Mohamed N. Abdelnabi verfasserin aut Mohamed N. Abdelnabi verfasserin aut Sabrina Mazouz verfasserin aut Sabrina Mazouz verfasserin aut Deborah Villafranca-Baughman verfasserin aut Deborah Villafranca-Baughman verfasserin aut Vincent Quoc-Huy Trinh verfasserin aut Shafi Muhammad verfasserin aut Shafi Muhammad verfasserin aut Nathalie Bédard verfasserin aut David Osorio Laverde verfasserin aut Ghada S. Hassan verfasserin aut Adriana Di Polo verfasserin aut Adriana Di Polo verfasserin aut Naglaa H. Shoukry verfasserin aut Naglaa H. Shoukry verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.994480 kostenfrei https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfieldsGer	10.3389/fimmu.2022.994480 doi (DE-627)DOAJ022188606 (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 DE-627 ger DE-627 rakwb eng RC581-607 Manuel Flores Molina verfasserin aut Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy Manuel Flores Molina verfasserin aut Mohamed N. Abdelnabi verfasserin aut Mohamed N. Abdelnabi verfasserin aut Sabrina Mazouz verfasserin aut Sabrina Mazouz verfasserin aut Deborah Villafranca-Baughman verfasserin aut Deborah Villafranca-Baughman verfasserin aut Vincent Quoc-Huy Trinh verfasserin aut Shafi Muhammad verfasserin aut Shafi Muhammad verfasserin aut Nathalie Bédard verfasserin aut David Osorio Laverde verfasserin aut Ghada S. Hassan verfasserin aut Adriana Di Polo verfasserin aut Adriana Di Polo verfasserin aut Naglaa H. Shoukry verfasserin aut Naglaa H. Shoukry verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.994480 kostenfrei https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfieldsSound	10.3389/fimmu.2022.994480 doi (DE-627)DOAJ022188606 (DE-599)DOAJ1a9adf263d8c472bbe8fcd4f23c43a10 DE-627 ger DE-627 rakwb eng RC581-607 Manuel Flores Molina verfasserin aut Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury. liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy Manuel Flores Molina verfasserin aut Mohamed N. Abdelnabi verfasserin aut Mohamed N. Abdelnabi verfasserin aut Sabrina Mazouz verfasserin aut Sabrina Mazouz verfasserin aut Deborah Villafranca-Baughman verfasserin aut Deborah Villafranca-Baughman verfasserin aut Vincent Quoc-Huy Trinh verfasserin aut Shafi Muhammad verfasserin aut Shafi Muhammad verfasserin aut Nathalie Bédard verfasserin aut David Osorio Laverde verfasserin aut Ghada S. Hassan verfasserin aut Adriana Di Polo verfasserin aut Adriana Di Polo verfasserin aut Naglaa H. Shoukry verfasserin aut Naglaa H. Shoukry verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.994480 kostenfrei https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
language	English
source	In Frontiers in Immunology 13(2022) volume:13 year:2022
sourceStr	In Frontiers in Immunology 13(2022) volume:13 year:2022
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Manuel Flores Molina @@aut@@ Mohamed N. Abdelnabi @@aut@@ Sabrina Mazouz @@aut@@ Deborah Villafranca-Baughman @@aut@@ Vincent Quoc-Huy Trinh @@aut@@ Shafi Muhammad @@aut@@ Nathalie Bédard @@aut@@ David Osorio Laverde @@aut@@ Ghada S. Hassan @@aut@@ Adriana Di Polo @@aut@@ Naglaa H. Shoukry @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ022188606
language_de	englisch
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callnumber-first	R - Medicine
author	Manuel Flores Molina
spellingShingle	Manuel Flores Molina misc RC581-607 misc liver misc macrophage misc acute injury misc CCl4 (carbon tetra chloride) misc Kupffer cell (KC) misc monocyte-derived macrophages misc Immunologic diseases. Allergy Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury
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topic_title	RC581-607 Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury liver macrophage acute injury CCl4 (carbon tetra chloride) Kupffer cell (KC) monocyte-derived macrophages
topic	misc RC581-607 misc liver misc macrophage misc acute injury misc CCl4 (carbon tetra chloride) misc Kupffer cell (KC) misc monocyte-derived macrophages misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc liver misc macrophage misc acute injury misc CCl4 (carbon tetra chloride) misc Kupffer cell (KC) misc monocyte-derived macrophages misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc liver misc macrophage misc acute injury misc CCl4 (carbon tetra chloride) misc Kupffer cell (KC) misc monocyte-derived macrophages misc Immunologic diseases. Allergy
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title	Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury
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title_full	Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury
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author_browse	Manuel Flores Molina Mohamed N. Abdelnabi Sabrina Mazouz Deborah Villafranca-Baughman Vincent Quoc-Huy Trinh Shafi Muhammad Nathalie Bédard David Osorio Laverde Ghada S. Hassan Adriana Di Polo Naglaa H. Shoukry
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title_sort	distinct spatial distribution and roles of kupffer cells and monocyte-derived macrophages in mouse acute liver injury
callnumber	RC581-607
title_auth	Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury
abstract	Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury.
abstractGer	Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury.
abstract_unstemmed	Macrophages are key regulators of inflammation and repair, but their heterogeneity and multiple roles in the liver are not fully understood. We aimed herein to map the intrahepatic macrophage populations and their function(s) during acute liver injury. We used flow cytometry, gene expression analysis, multiplex-immunofluorescence, 3D-reconstruction, and spatial image analysis to characterize the intrahepatic immune landscape in mice post-CCl4-induced acute liver injury during three distinct phases: necroinflammation, and early and late repair. We observed hepatocellular necrosis and a reduction in liver resident lymphocytes during necroinflammation accompanied by the infiltration of circulating myeloid cells and upregulation of inflammatory cytokines. These parameters returned to baseline levels during the repair phase while pro-repair chemokines were upregulated. We identified resident CLEC4F+ Kupffer cells (KCs) and infiltrating IBA1+CLEC4F- monocyte-derived macrophages (MoMFs) as the main hepatic macrophage populations during this response to injury. While occupying most of the necrotic area, KCs and MoMFs exhibited distinctive kinetics, distribution and morphology at the site of injury. The necroinflammation phase was characterized by low levels of KCs and a remarkable invasion of MoMFs suggesting their potential role in phagoctosing necrotic hepatocytes, while opposite kinetics/distribution were observed during repair. During the early repair phase, yolksac - derived KCs were restored, whereas MoMFs diminished gradually then dissipated during late repair. MoMFs interacted with hepatic stellate cells during the necroinflammatory and early repair phases, potentially modulating their activation state and influencing their fibrogenic and pro-repair functions that are critical for wound healing. Altogether, our study reveals novel and distinct spatial and temporal distribution of KCs and MoMFs and provides insights into their complementary roles during acute liver injury.
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title_short	Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury
url	https://doi.org/10.3389/fimmu.2022.994480 https://doaj.org/article/1a9adf263d8c472bbe8fcd4f23c43a10 https://www.frontiersin.org/articles/10.3389/fimmu.2022.994480/full https://doaj.org/toc/1664-3224
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author2Str	Manuel Flores Molina Mohamed N. Abdelnabi Sabrina Mazouz Deborah Villafranca-Baughman Vincent Quoc-Huy Trinh Shafi Muhammad Nathalie Bédard David Osorio Laverde Ghada S. Hassan Adriana Di Polo Naglaa H. Shoukry
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up_date	2024-07-04T00:34:30.234Z
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Distinct spatial distribution and roles of Kupffer cells and monocyte-derived macrophages in mouse acute liver injury

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