Abstract
Monocytes develop in the bone marrow from the hematopoietic stem cells and represent heterogeneous phagocyte cells in the circulation. In homeostatic and inflammatory conditions, after recruitment into tissues, monocytes differentiate into macrophages and dendritic cells. Alcohol use causes about 3.3 million worldwide deaths per year, which is about 5.9% of all deaths. In the United States and Europe, alcohol use disorders represent the fifth leading cause of death. Females are more susceptible to alcoholic liver injury in both humans and mice. Strikingly, we still do not know how much of this difference in tissue injury is due to the differential effect of alcohol and its toxic metabolites on a) parenchymal or resident cells and/or b) immune response to alcohol. Therefore, we used a model of chronic alcohol exposure in mice to investigate the dynamics of monocytes, an innate immune cell type showed to be critical in alcoholic liver injury, by using immunophenotypic characterization. Our data reveal a sex-dimorphism of alcohol response of hepatic monocytes in female mice that is interferon receptor alpha dependent. This dimorphism could shed light on potential cellular mechanism(s) to explain the susceptibility of females to alcoholic immunopathogenesis and suggests an additional targetable pathway for alcoholic liver injury in females.
Highlights
Monocytes originate in the bone marrow (BM) from the hematopoietic stem cells and represent a heterogeneous population of phagocytes in the circulation [1, 2]
We chose MC, not Lieber DeCarli (LD), the most common mouse model of chronic alcoholic liver injury, because we are interested in studying the specific effect of alcohol on immune cells without the interference of the high fat and liquid diet used in LD model
Four weeks of alcohol consumption caused a significant reduction in the body weight, but not liver weight, of male mice; normalized liver/body weight ratio, surrogate for steatosis development, showed a significant increase only in female mice compared to controls (Supplementary Figures 1A–C)
Summary
Monocytes originate in the bone marrow (BM) from the hematopoietic stem cells and represent a heterogeneous population of phagocytes in the circulation [1, 2]. In homeostatic and inflammatory conditions, after recruitment into tissues, monocytes differentiate into macrophages and dendritic cells (DC) [1, 2]. In both humans and mice, monocytes are classified into subsets based on differential expression of specific markers and function [3,4,5]. The locally patrolling monocytes (pro-repair) express high levels of CX3CR1 but low levels of both Ly-6C and CCR2 and described phenotypically as Ly-6CloCX3CR1hi [1, 2, 4, 5]
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