The impact of G-CSF on mouse immune cells in alcoholic liver disease, focusing on variations in T cells and their subsets

Biomed Pharmacother. 2024 Sep:178:117175. doi: 10.1016/j.biopha.2024.117175. Epub 2024 Jul 28.

Abstract

Alcoholic liver disease (ALD) significantly affects immune cell function and leads to immunological dysregulation. This study explored the potential of granulocyte colony-stimulating factor (G-CSF) to mitigate the negative effects of alcohol on immune cells in a mouse model of ALD. To investigate the capacity of G-CSF, ALD was induced using a 17-day alcohol-enriched diet, followed by a single G-CSF dose prior to sampling. We focused on the dynamics of peripheral blood mononuclear cells using high-dimensional mass cytometry to detect subtle changes. Alcohol intake reduced the number of B cells, monocytes, dendritic cells, and NK cells while increasing the number of T cells. Notably, G-CSF treatment reversed the alcohol-induced increase in total CD4+ and CD8+ T cell populations. This effect was remarkable in naïve, effector CD4+ T cells and naïve CD8+ T cells. PhenoGraph and FlowSOM analysis further revealed the recovery effect of G-CSF on specific T cell subgroups, including central memory CD8+ T cells and double-negative T cells expressing Ly6chighCD44high, which are adversely affected by alcohol. These results enhance our understanding of the effect of ALD on immune function and suggest that G-CSF is a potential therapeutic agent, laying the foundation for future clinical research.

Keywords: ALD; Granulocyte; Granulocyte colony-stimulating factor (G-CSF); Mass cytometry; T cell.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Models, Animal
  • Ethanol / pharmacology
  • Granulocyte Colony-Stimulating Factor* / pharmacology
  • Liver Diseases, Alcoholic* / drug therapy
  • Liver Diseases, Alcoholic* / immunology
  • Liver Diseases, Alcoholic* / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology

Substances

  • Ethanol
  • Granulocyte Colony-Stimulating Factor