#3636 INHIBITION OF THE STING PATHWAY AMELIORATES EXPERIMENTAL CRESCENTIC GLOMERULONEPHRITIS

Abstract Background and Aims Rapidly progressive glomerulonephritis/crescentic glomerulonephritis (RPGN/cGN) may compromise renal function in the short or medium term thus evolving into acute kidney injury (AKI) chronic disease. Innate adaptive immune responses are placed at epicentre of cGN. However, molecular pathways involved activation these by far less known. Sting is an innate DNA-sensing promoting fibrosis with unknown participation RPGN/cGN. Method We investigated whether pathway contributes to development progression RPGN/cGN a preclinical model nephrotoxic nephritis (NTN) induced anti-glomerular basal membrane serum. expression as well humoral cellular responses, histological functional were studied wild-type Sting-/- mice. Results was found expressed higher gene protein levels located tubulointerstitial intraglomerular periglomerular areas tubules kidneys from NTN mice compared non-diseased control animals. deficiency significantly decreased NTN-induced cytokine/chemokine synthesis hence intrarenal transit both mononuclear phagocytes overall specific T-cell subsets. Sting-deficient also displayed extensive affection, namely fewer number glomerular crescents associated lesions (sclerosis, endocapillary hypercellularity/sinaquiae), tubular injury. The presence TUNEL-positive dead cells reduced Consistent findings, absence diminished NTN-increased urea creatinine plasma levels. Conclusion inhibition positively impacted several well-characterized cGN-associated pathogenic events ameliorating outcomes These results identified antagonism potential therapy help combat