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bioRxiv · 10.64898/2026.11.07.765085

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

Kazimierczyk, D.·Seed, B.·Jain, N.
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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.

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Kazimierczyk, D., Seed, B., Jain, N.. 2026-11-10. Systemic TLR7 agonism moderates disease severity in acute DSS-induced colitis in mice. https://doi.org/10.64898/2026.11.07.765085

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