Glutamine metabolism as a rheostat of CD4(+) T cell pathogenic function in metabolic dysfunction-associated steatotic liver disease.

Hepatic glutamine metabolism critically regulates pathogenic CD4(+) T cell inflammation, with Gln depletion linked to increased liver damage in MASLD.

• Why it matters: Understanding how immune cell metabolism influences disease progression can reveal new therapeutic targets for MASLD, a condition with limited treatment options.
• What they did: The study examined hepatic Gln levels in humans and mice, used Gln supplementation to assess effects on T cell inflammation, and explored mechanisms involving Gls1-mediated glutaminolysis and O-GlcNAcylation.
• The result: Restoring hepatic Gln reduced CD4(+) T cell inflammation and liver damage, suggesting metabolism-targeted strategies could slow MASLD progression by modulating immune responses.