Division of Digestive Diseases and Nutrition, Section of Hepatology, Rush University, Chicago, IL, United States.
Front Immunol. 2021 Apr 30;12:663548. doi: 10.3389/fimmu.2021.663548. eCollection 2021.
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.
单核细胞由造血干细胞在骨髓中发育而来，代表循环中异质性的吞噬细胞。在稳态和炎症条件下，单核细胞被募集到组织中后，会分化为巨噬细胞和树突状细胞。饮酒每年导致全球约 330 万人死亡，约占所有死亡人数的 5.9%。在美国和欧洲，酒精使用障碍是导致死亡的第五大原因。在人类和小鼠中，女性对酒精性肝损伤更敏感。令人惊讶的是，我们仍然不知道组织损伤的这种差异有多少是由于酒精及其有毒代谢物对 a）实质或常驻细胞和/或 b）对酒精的免疫反应的差异作用造成的。因此，我们使用慢性酒精暴露在小鼠中的模型，通过免疫表型特征来研究先天免疫细胞单核细胞的动态变化，该细胞类型被证明在酒精性肝损伤中至关重要。我们的数据揭示了雌性小鼠肝单核细胞对酒精反应的性别二态性，这依赖于干扰素受体 alpha。这种二态性可以揭示潜在的细胞机制，以解释女性对酒精性免疫发病机制的易感性，并为女性的酒精性肝损伤提供了另一个可靶向的途径。
