Chronic Alcohol Consumption Expands Bone Marrow Myelopoiesis While Suppressing Splenic Hematopoiesis

Chronic alcohol consumption-mediated immune dysregulation elevates the risk of multiple diseases, yet how these immunological alterations manifest across tissues remains poorly understood. Here, we investigated the impact of chronic alcohol consumption on hematopoiesis and immune homeostasis across the bone marrow (BM), spleen (SP), and peripheral blood (PB) using female C57BL/6 mice fed a Lieber-DeCarli liquid diet with 6% (v/v) ethanol for 6 weeks. Alcohol consumption induced a mild hepatic injury, evidenced by increased liver weight, elevated plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and hepatic steatosis without fibrosis. Immune phenotyping by high-dimensional spectral flow cytometry showed that, in the BM, alcohol expanded myeloid-biased multipotent progenitors 2 and 3 (MPP2 and MPP3), granulocyte-monocyte progenitors (GMPs), and macrophages. Conversely, the SP exhibited reduced abundance and proliferative activity of lineage-negative c-KIT-positive (LK) and megakaryocyte-erythroid progenitor (MEP) populations, resulting in impaired erythropoiesis. Despite these tissue-specific alterations, PB exhibited comparatively subtle and more variable changes than the BM and SP. These findings demonstrate that alcohol-mediated hematopoietic remodeling is tissue-specific and may not be fully captured by PB analyses. They further highlight the potential need for improved tissue-informed biomarkers and diagnostic approaches to detect and monitor alcohol-mediated immune remodeling beyond PB.