Chronic inflammation drives diabetic nephropathy, a major cause of chronic kidney disease. At EASD 2025, researchers presented findings implicating transducin-like enhancer of split 4 (TLE4) as a key regulator of cGAS-STING-mediated inflammation in type 2 diabetes.

Clinical data from 1,940 patients (714 with diabetic nephropathy) revealed that elevated inflammatory indices—neutrophil-to-lymphocyte ratio, neutrophil-to-high-density lipoprotein ratio, and systemic inflammation response index—were independently associated with increased disease risk. Bioinformatic analyses of kidney datasets confirmed reduced TLE4 expression in diabetic nephropathy. 

In vitro, palmitic acid–treated renal tubular cells exhibited suppressed TLE4 and activation of cGAS-STING signaling. Silencing TLE4 further amplified inflammatory cytokine release. Co-immunoprecipitation, immunofluorescence, and AlphaFold modeling demonstrated direct, high-affinity binding between TLE4 and STING.

These findings reveal a TLE4-dependent mechanism linking metabolic stress to renal inflammation. Targeting TLE4 or its interaction with STING may offer a novel therapeutic strategy to reduce inflammation and protect kidney function in diabetes.