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Nat Commun ; 12(1): 1770, 2021 03 19.
Article in English | MEDLINE | ID: mdl-33741914

ABSTRACT

Inflammation generally leads to recruitment of monocyte-derived macrophages. What regulates the fate of these cells and to what extent they can assume the identity and function of resident macrophages is unclear. Here, we show that macrophages elicited into the peritoneal cavity during mild inflammation persist long-term but are retained in an immature transitory state of differentiation due to the presence of enduring resident macrophages. By contrast, severe inflammation results in ablation of resident macrophages and a protracted phase wherein the cavity is incapable of sustaining a resident phenotype, yet ultimately elicited cells acquire a mature resident identity. These macrophages also have transcriptionally and functionally divergent features that result from inflammation-driven alterations to the peritoneal cavity micro-environment and, to a lesser extent, effects of origin and time-of-residency. Hence, rather than being predetermined, the fate of inflammation-elicited peritoneal macrophages seems to be regulated by the environment.


Subject(s)
Cell Differentiation/genetics , Inflammation/genetics , Macrophages, Peritoneal/metabolism , Macrophages/metabolism , Peritoneal Cavity/pathology , Animals , Cells, Cultured , Cytokines/metabolism , Female , GATA6 Transcription Factor/genetics , GATA6 Transcription Factor/metabolism , Gene Expression Profiling , Inflammation/metabolism , Macrophages/cytology , Macrophages, Peritoneal/cytology , Male , Mice, Congenic , Mice, Inbred C57BL , Peritonitis/genetics , Peritonitis/metabolism
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