unconjugated bilirubin

Unconjugated bilirubin (UCB) is a metabolic byproduct of heme catabolism that functions as an endogenous immunomodulator. Traditionally viewed as a waste product, UCB has been identified as an agonist of the aryl hydrocarbon receptor (AhR), a critical modulator of adaptive immunity. UCB exerts its immunoregulatory effects by downregulating glycolysis-related genes, specifically phosphoglycerate kinase 1 (PGK1) and aldolase A (ALDOA), and by upregulating the ectonucleotidase CD39. This metabolic reprogramming in Th17 cells leads to a reduction in the extracellular acidification rate and oxygen consumption rate, effectively suppressing the production of pro-inflammatory cytokines such as IL-17 while boosting regulatory markers like Tim-3. Research indicates that these UCB-mediated pathways are defective in patients with Crohn's disease, suggesting that UCB or strategies targeting these metabolic checkpoints could serve as therapeutic tools for restoring immune homeostasis in inflammatory bowel diseases and other autoimmune conditions.

Other names

indirect bilirubinfree bilirubin