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No distinct cluster-specific regulatory pathways were detected in MES

Conversely, we define Treg exhaustion more specifically as a state induced by chronic inflammation, characterized by persistent expression of inhibitory receptors (e.g., PD-1/TIGIT), metabolic insufficiency, epigenetic and lineage instability (such as FOXP3 destabilization), and a decline in suppressive capacity, particularly in the context of continuous antigenic and cytokine stimulation

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This is because prostaglandins, which are blocked by COX inhibition, are important for proper blood vessel function within the kidneys (Ejaz 2004)