COMMD10 is critical for Kupffer cell survival and controls Ly6Chi monocyte differentiation and inflammation in the injured liver
Summary: Liver-resident macrophages Kupffer cells (KCs) and infiltrating Ly6Chi monocytes both contribute to liver tissue regeneration in various pathologies but also to disease progression upon disruption of orderly consecutive regeneration cascades. Little is known about molecular pathways that re...
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Elsevier
2021
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oai:doaj.org-article:fe477e9d24474de1a974c2e01f7c0b012021-11-18T04:48:02ZCOMMD10 is critical for Kupffer cell survival and controls Ly6Chi monocyte differentiation and inflammation in the injured liver2211-124710.1016/j.celrep.2021.110026https://doaj.org/article/fe477e9d24474de1a974c2e01f7c0b012021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721015084https://doaj.org/toc/2211-1247Summary: Liver-resident macrophages Kupffer cells (KCs) and infiltrating Ly6Chi monocytes both contribute to liver tissue regeneration in various pathologies but also to disease progression upon disruption of orderly consecutive regeneration cascades. Little is known about molecular pathways that regulate their differentiation, maintenance, or inflammatory behavior during injury. Here, we show that copper metabolism MURR1 domain (COMMD)10-deficient KCs adopt liver-specific identity. Strikingly, COMMD10 deficiency in KCs and in other tissue-resident macrophages impedes their homeostatic survival, leading to their continuous replacement by Ly6Chi monocytes. While COMMD10 deficiency in KCs mildly worsens acetaminophen-induced liver injury (AILI), its deficiency in Ly6Chi monocytes results in exacerbated and sustained hepatic damage. Monocytes display unleashed inflammasome activation and a reduced type I interferon response and acquire “neutrophil-like” and lipid-associated macrophage differentiation fates. Collectively, COMMD10 appears indispensable for KC and other tissue-resident macrophage survival and is an important regulator of Ly6Chi monocyte fate decisions and reparative behavior in the diseased liver.Keren CohenOdelia MouhadebShani Ben ShlomoMarva LangerAnat NeumannNoam ErezItay MoshkovitsRotem PeletDaniel J. KedarEli BrazowskiMartin GuilliamsHelen S. GoodridgeNathan GluckChen VarolElsevierarticleCOMMD10Kupffer cellsLy6Chi monocytesneutrophil-like monocytesdendritic cell like monocyteslipid-associated macrophagesBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 7, Pp 110026- (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
COMMD10 Kupffer cells Ly6Chi monocytes neutrophil-like monocytes dendritic cell like monocytes lipid-associated macrophages Biology (General) QH301-705.5 |
| spellingShingle |
COMMD10 Kupffer cells Ly6Chi monocytes neutrophil-like monocytes dendritic cell like monocytes lipid-associated macrophages Biology (General) QH301-705.5 Keren Cohen Odelia Mouhadeb Shani Ben Shlomo Marva Langer Anat Neumann Noam Erez Itay Moshkovits Rotem Pelet Daniel J. Kedar Eli Brazowski Martin Guilliams Helen S. Goodridge Nathan Gluck Chen Varol COMMD10 is critical for Kupffer cell survival and controls Ly6Chi monocyte differentiation and inflammation in the injured liver |
| description |
Summary: Liver-resident macrophages Kupffer cells (KCs) and infiltrating Ly6Chi monocytes both contribute to liver tissue regeneration in various pathologies but also to disease progression upon disruption of orderly consecutive regeneration cascades. Little is known about molecular pathways that regulate their differentiation, maintenance, or inflammatory behavior during injury. Here, we show that copper metabolism MURR1 domain (COMMD)10-deficient KCs adopt liver-specific identity. Strikingly, COMMD10 deficiency in KCs and in other tissue-resident macrophages impedes their homeostatic survival, leading to their continuous replacement by Ly6Chi monocytes. While COMMD10 deficiency in KCs mildly worsens acetaminophen-induced liver injury (AILI), its deficiency in Ly6Chi monocytes results in exacerbated and sustained hepatic damage. Monocytes display unleashed inflammasome activation and a reduced type I interferon response and acquire “neutrophil-like” and lipid-associated macrophage differentiation fates. Collectively, COMMD10 appears indispensable for KC and other tissue-resident macrophage survival and is an important regulator of Ly6Chi monocyte fate decisions and reparative behavior in the diseased liver. |
| format |
article |
| author |
Keren Cohen Odelia Mouhadeb Shani Ben Shlomo Marva Langer Anat Neumann Noam Erez Itay Moshkovits Rotem Pelet Daniel J. Kedar Eli Brazowski Martin Guilliams Helen S. Goodridge Nathan Gluck Chen Varol |
| author_facet |
Keren Cohen Odelia Mouhadeb Shani Ben Shlomo Marva Langer Anat Neumann Noam Erez Itay Moshkovits Rotem Pelet Daniel J. Kedar Eli Brazowski Martin Guilliams Helen S. Goodridge Nathan Gluck Chen Varol |
| author_sort |
Keren Cohen |
| title |
COMMD10 is critical for Kupffer cell survival and controls Ly6Chi monocyte differentiation and inflammation in the injured liver |
| title_short |
COMMD10 is critical for Kupffer cell survival and controls Ly6Chi monocyte differentiation and inflammation in the injured liver |
| title_full |
COMMD10 is critical for Kupffer cell survival and controls Ly6Chi monocyte differentiation and inflammation in the injured liver |
| title_fullStr |
COMMD10 is critical for Kupffer cell survival and controls Ly6Chi monocyte differentiation and inflammation in the injured liver |
| title_full_unstemmed |
COMMD10 is critical for Kupffer cell survival and controls Ly6Chi monocyte differentiation and inflammation in the injured liver |
| title_sort |
commd10 is critical for kupffer cell survival and controls ly6chi monocyte differentiation and inflammation in the injured liver |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/fe477e9d24474de1a974c2e01f7c0b01 |
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