Lanthionine synthetase C-like 2 (LANCL2) therapeutics have gained increasing recognition as a novel treatment modality for a wide range of autoimmune diseases. Genetic ablation of LANCL2 in mice results in severe inflammatory phenotypes in inflammatory bowel disease (IBD) and lupus. Pharmacological activation of LANCL2 provides therapeutic efficacy in mouse models of intestinal inflammation, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and psoriasis. Mechanistically, LANCL2 activation enhances regulatory CD4 + T cell (Treg) responses and downregulates effector responses in the gut. The stability and suppressive capacities of Treg cells are enhanced by LANCL2 activation through engagement of immunoregulatory mechanisms that favor mitochondrial metabolism and amplify IL-2/CD25 signaling. Omilancor, the most advanced LANCL2 immunoregulatory therapeutic in late-stage clinical development, is a phase 3 ready, first-in-class, gut-restricted, oral, once-daily, small-molecule therapeutic in clinical development for the treatment of UC and CD. In this review, we discuss this novel mechanism of mucosal immunoregulation and how LANCL2-targeting therapeutics could help address the unmet clinical needs of patients with autoimmune diseases, starting with IBD.
The NIMML Institute and NImmune Biopharma Announce Publication of New Mechanistic Insights on the Immunometabolic Control of Systemic Lupus Erythematosus in the Journal of Immunology
The NIMML Institute and NImmune Biopharma Announce Publication of New Mechanistic Insights on the Immunometabolic Control of Systemic Lupus Erythematosus in the Journal of Immunology
Download Press Release NIM-1324 validated as the first LANCL2 drug with therapeutic efficacy in systemic inflammation in three mouse models of lupus to support immune tolerance A mechanism of LANCL2 newly discovered in phagocytes that combines with established...
