I am a
Home I AM A Search Login

Papers of the Week

Papers: 17 Sep 2022 - 23 Sep 2022

2022 Sep 21

Commun Biol



Blockade of PGK1 and ALDOA enhances bilirubin control of Th17 cells in Crohn’s disease.


Vuerich M, Wang N, Graham JJ, Gao L, Zhang W, Kalbasi A, Zhang L, Csizmadia E, Hristopoulos J, Ma Y, Kokkotou E, Cheifetz AS, Robson SC, Longhi M S
Commun Biol. 2022 Sep 21; 5(1):994.
PMID: 36131123.


Unconjugated bilirubin (UCB) confers Th17-cells immunosuppressive features by activating aryl-hydrocarbon-receptor, a modulator of toxin and adaptive immune responses. In Crohn's disease, Th17-cells fail to acquire regulatory properties in response to UCB, remaining at an inflammatory/pathogenic state. Here we show that UCB modulates Th17-cell metabolism by limiting glycolysis and through downregulation of glycolysis-related genes, namely phosphoglycerate-kinase-1 (PGK1) and aldolase-A (ALDOA). Th17-cells of Crohn's disease patients display heightened PGK1 and ALDOA and defective response to UCB. Silencing of PGK1 or ALDOA restores Th17-cell response to UCB, as reflected by increase in immunoregulatory markers like FOXP3, IL-10 and CD39. In vivo, PGK1 and ALDOA silencing enhances UCB salutary effects in trinitro-benzene-sulfonic-acid-induced colitis in NOD/scid/gamma humanized mice where control over disease activity and enhanced immunoregulatory phenotypes are achieved. PGK1 and/or ALDOA blockade might have therapeutic effects in Crohn's disease by favoring acquisition of regulatory properties by Th17-cells along with control over their pathogenic potential.