We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Blockade of PGK1 and ALDOA enhances bilirubin control of Th17 cells in Crohn's disease.
- Authors
Vuerich, Marta; Wang, Na; Graham, Jonathon J.; Gao, Li; Zhang, Wei; Kalbasi, Ahmadreza; Zhang, Lina; Csizmadia, Eva; Hristopoulos, Jason; Ma, Yun; Kokkotou, Efi; Cheifetz, Adam S.; Robson, Simon C.; Longhi, Maria Serena
- Abstract
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. Unconjugated bilirubin modulates Th17-cell metabolism in Crohn's disease by limiting glycolysis and through downregulation of phosphoglycerate-kinase-1 (PGK1) and aldolase-A (ALDOA).
- Publication
Communications Biology, 2022, Vol 5, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-022-03913-9