Hepatic cholinergic T cell signaling mediates an adaptive response to alcohol-induced liver stress
Knights, A. J.; Liu, S.; Kim, E. J.; Wu, J.
Show abstract
Alcohol-associated liver disease (ALD) is a major cause of liver-related morbidity and mortality, yet no targeted, disease-modifying therapy exists and the immune mechanisms driving disease progression remain poorly defined. Acetylcholine-producing cholinergic immune cells have emerged as regulators of homeostasis across tissues and in disease, but their role in alcohol-induced hepatic stress is unknown. Here, we characterized the hepatic cholinergic immune landscape during alcohol-induced stress using flow cytometry and single-cell RNA-sequencing of ChAT-eGFP reporter mice. Alcohol feeding expanded hepatic cholinergic immune cells, with T cells constituting a substantial and dynamic fraction of this population that showed a broad increase in acetylcholine signaling and shifted towards a repressed, anergy-like transcriptional state. CD4 T cells underwent coordinated suppression of cholesterol biosynthesis, while CD8 T cells instead adopted a cytotoxic activation program. Together, these findings identify cholinergic T cell signaling, and cholesterol metabolism within CD4 T cells specifically, as a previously unrecognized adaptive response to alcohol-induced liver stress, nominating candidate therapeutic targets for a disease that is marred by critically limited treatment options.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The hepatic compensatory response to elevated systemic sulfide promotes diabetes 92%
- Liver Receptor Homolog-1 (LRH-1/NR5A2) orchestrates hepatic inflammation and TNF-induced cell death 92%
- Integration of metabolomic and transcriptomic analyses reveals novel regulatory functions of the ChREBP transcription factor in energy metabolism 92%
Similar papers in this journal
- Gut Microbial Trimethylamine is Elevated in Alcohol-Associated Hepatitis and Contributes to Ethanol-Induced Liver Injury in Mice 94%
- Membrane Bound O-Acyltransferase 7 (MBOAT7) Shapes Lysosomal Lipid Homeostasis and Function to Control Alcohol-Associated Liver Injury 94%
- Hyperactivated Glycolysis Drives Spatially-Patterned Kupffer Cell Depletion in MASLD 94%
Similar papers in this journal
- Liver Sinusoidal Endothelial Cells and Laminin dictate cholangiocytes fate in chronic liver disease 91%
- RORc expressing immune cells negatively regulate tertiary lymphoid structure formation and support their pro-tumorigenic functions 91%
- Mendelian Randomization Analysis Dissects the Relationship between NAFLD, T2D, and Obesity and Provides Implications to Precision Medicine 90%
Similar papers in this journal
Similar papers in this journal
- Autocrine IL11 cis-signaling in hepatocytes is an initiating nexus between lipotoxicity and non-alcoholic steatohepatitis 92%
- Liver-innervating vagal sensory neurons play an indispensable role in the development of hepatic steatosis and anxiety-like behavior in mice fed a high-fat diet. 92%
- A sexually dimorphic hepatic cycle of periportal VLDL generation and subsequent pericentral VLDLR-mediated lipoprotein re-uptake 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.