Oleic Acid Promotes Treg Cell Differentiation via Autophagy Induction and Ameliorates DSS-Induced Colitis

Oleic acid (OA), a monounsaturated fatty acid (FA) prevalent in olive oil and key component of Mediterranean diet, exhibits anti-inflammatory effects in ulcerative colitis (UC), but its immunomodulatory mechanisms remain largely elusive. Here, we found that OA promotes T regulatory cell (Treg) differentiation in a dose-dependent manner. OA inhibited the activation of the mechanistic target of rapamycin complex 1 (mTORC1) while simultaneously promoting AMP-activated protein kinase (AMPK) activity, both of which are essential for the autophagy pathway. Notably, blockade of autophagy abolished OA-induced Treg differentiation, indicating that autophagy was essential for the immunomodulatory effects of OA. In a dextran sulfate sodium (DSS)-induced colitis model, OA administration significantly increased colonic CD4⁺Foxp3⁺ Treg populations and ameliorated disease severity, including reduced weight loss, bleeding, and histological damage. In summary, our findings revealed that OA promoted Treg differentiation both in vitro and in vivo, suggesting that OA or diets rich in this FA could be promising supplementary therapies for UC.