Systemic TLR7 agonism moderates disease severity in acute DSS-induced colitis in mice
Year: 2026
Type: preprint
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.
Authors: Daniel Kazimierczyk, Brian Seed, Nitya Jain
Institutions: Massachusetts General Hospital, Mass General Brigham
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225753104
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