Validation of a novel E3 ligase of GILZ as a glucocorticoid-sparing therapeutic target in SLE

Glucocorticoids are very effective at treating inflammation, however, they also cause toxic side effects. Glucocorticoids are particularly harmful in the autoimmune disease, systemic lupus erythematosus (SLE), where they increase the accumulation of organ damage over time. The glucocorticoid-induced leucine zipper (GILZ) has the same broad immunosuppressive effects as GCs but is independent their side effects. We investigated a method for boosting GILZ by inhibiting a protein which causes its degradation: “E3-X”. Deleting E3-X increased GILZ, suppressed inflammation and demonstrated minimal potential for harmful side effects. This paves the way for the development of therapies inhibiting E3-X to reduce glucocorticoid use in SLE and across medicine in general.