Oleic acid restores suppressive defects in tissue-resident FOXP3 Tregs from patients with multiple sclerosis.

ABSTRACT: FOXP3+ Tregs rely on fatty acid β-oxidation-driven (FAO-driven) oxidative phosphorylation (OXPHOS) for differentiation and function. Recent data demonstrate a role for Tregs in the maintenance of tissue homeostasis, with tissue-resident Tregs possessing tissue-specific transcriptomes. However, specific signals that establish tissue-resident Treg programs remain largely unknown. Tregs metabolically rely on FAO, and considering the lipid-rich environments of tissues, we hypothesized that environmental lipids drive Treg homeostasis. First, using human adipose tissue to model tissue residency, we identified oleic acid as the most prevalent free fatty acid. Mechanistically, oleic acid amplified Treg FAO-driven OXPHOS metabolism, creating a positive feedback mechanism that increased the expressi

SUBMITTER: Pompura SL 

PROVIDER: S-EPMC7810477 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature