Effect of panobinostat, givinostat and ruxolitinib treatment in the anti-GBM mouse model of crescentic glomerulonephritis.

We demonstrated that in anti-glomerular basement membrane (anti-GBM) glomerulonephritis, crescents derived from clonal amplification of an immature subset of parietal epithelial cells (PECs) and that following treatment of mice with 3 different drugs currently used in haematological stem cell disorders (panobinostat, givinostat and ruxolitinib), only panobinostat exerted beneficial effect. To establish the mechanism of action of panobinostat, we generated single-cell RNA sequencing (scRNAseq) datasets of kidney cells obtained from control mice with anti-GBM glomerulonephritis and of mice treated with the three drugs. The analysis demonstrated that the drugs exerted similar effects on clusters of cells of the immune system, suggesting that all the three drugs elicit similar anti-inflammatory and immunosuppressive properties. Overall design: Establish the mechanism of the effect of panobinostat, givinostat and ruxolitinib treatment in the anti-GBM mouse model of crescentic glomerulonephritis