Fig. 4: ABHD11 inhibition drives sterol metabolism to modulate T-cell effector functions.
From: Mitochondrial ABHD11 inhibition drives sterol metabolism to modulate T-cell effector function
a Schematic overview of the mechanism through which ABHD11 inhibition suppresses T-cell effector function. ABHD11 activity is required for the conversion of α-ketoglutarate (α-KG) to succinyl-CoA. The TCA cycle becomes compromised following ABHD11 inhibition, resulting in increased levels of acetyl-CoA and lactate. Increased lactate drives SREBP2 activation, which together with increased acetyl-CoA levels promotes sterol metabolism, particularly the generation of 24,25-epoxycholesterol (24,25-EC) via the shunt pathway. Liver X receptor (LXR) activation increases in response to increased levels of 24,25-EC, which ultimately suppresses T-cell effector functions including cytokine production.
