Systemic TLR7 agonism moderates disease severity in acute DSS-induced colitis in mice

Abstract

Toll-like receptor 7 (TLR7) is an endosomal sensor of single-stranded RNA, studied for its antiviral and pro-inflammatory functions. Its role in intestinal inflammation is undefined, and no approved or clinical-stage therapy for inflammatory bowel disease (IBD) engages this pathway. Here we report that systemic administration of the reference TLR7 agonist GS-9620 (vesatolimod) moderates disease severity in acute dextran sodium sulfate (DSS)-induced colitis in mice. GS-9620-treated mice lost less weight, had lower Disease Activity Index scores, and were protected from DSS-induced colon shortening. Immunophenotyping of the spleen showed reduced Th17 and Tr17 populations and an increased proportion of regulatory T cells. These findings indicate that pharmacological TLR7 agonism is not merely tolerated in the inflamed intestine but is associated with a shift of the systemic immune compartment toward a regulatory phenotype. The results identify TLR7 as a candidate disease-moderating target in IBD and motivate direct tests of causality, route and chronic-disease relevance.