Resolvin E1 limits cyclosporine-induced toxicity and drives durable recovery in autoimmune bone marrow failure

Severe aplastic anemia (SAA), a lethal autoimmune disease and bone marrow failure disorder, exemplifies this challenge with its first-line therapy Cyclosporine A (CsA). CsA suppresses pathogenic T cells and partially restores hematopoiesis in the context of murine SAA, but is associated with nephrotoxicity, hepatotoxicity, and increased Th17 cells one month post-treatment.

Conversely, the pro-resolving lipid mediator Resolvin E1 (RvE1) prevents SAA-induced mortality, while also reducing inflammatory immune activation and preserving tissue homeostasis. Treatment with both CsA and RvE1 achieved 100% survival, restored hematopoietic and immune homeostasis, and mitigated CsA-induced toxicity. Mechanistically, RvE1 required the GPCR ChemR23 on immune cells to reverse CsA-induced inflammation and immune dysregulation.