Activation of V-Domain Immunoglobulin Suppressor of T-Cell Activation by Baloxavir Marboxil Ameliorates Systemic Lupus Erythematosus through Inhibiting Lysophosphatidylcholine/CD40 Ligand

• DOI: 10.1021/acs.chemrestox.4c00449
• Publication Date: 2025-01-08T17:05:01Z
• Authors: Zhijie Luo; Tingting Zhang; Penglu Wang; Dingyi Yuan; Shasha Jin; Jianwen Di; Ruixue Ma; Lu Yang; Xinzhi Wang; Jun Liu
• Keywords: Lysophosphatidylcholine

Deficiency of the V-domain immunoglobulin suppressor T-cell activation (VISTA) accelerates disease progression in lupus-prone mice, and VISTA shows therapeutic effects mouse models a lupus-like disease. Metabolic reprogramming T cells systemic lupus erythematosus (SLE) patients is important regulating function progression. However, mechanism by which affects immunometabolism SLE remains unclear. Here, we demonstrated that deficiency promoted synthesis metabolite lysophosphatidylcholine (LPC) using untargeted metabolomics increased protein expression CD40 ligand (CD40L). Furthermore, baloxavir marboxil (BXM), small molecule agonist VISTA, significantly ameliorated autoantibody production, renal damage, imbalance immune cell subpopulations mice (chronic graft-versus-host MRL/MpJ-Faslpr/J mice) possibly inhibiting LPC to downregulate CD40L aberrant noncanonical nuclear factor-κB pathway. Our results indicated BXM targeting symptoms altering lipid metabolism expression, offers novel mechanisms promising therapy for SLE.