ArticleMolecular biology reports2026
IL-22 modulates STAT3/β-catenin/let-7a signaling and hepatic granulomas in Schistosoma mansoni infection: versus praziquantel and combination treatment.
Article in Molecular biology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHepatic granuloma formation in Schistosoma mansoni infection is driven by dysregulated cytokine networks and pro-fibrotic signaling pathways, including STAT3, Wnt/β-catenin, and microRNA let-7a circuits. Interleukin-22 (IL-22) is an epithelial-targeted cytokine that signals predominantly through STAT3 and has been implicated in tissue protection and fibrosis modulation. This investigation examined whether IL-22 modulates the STAT3/β-catenin/let-7a molecular axis in schistosomal hepatic granulomas and compared these molecular effects with praziquantel (PZQ) anthelmintic therapy.
methodsMale mice infected with S. mansoni were treated with recombinant IL-22 (0.36 µg/kg intraperitoneally for 14 days), a single oral dose of praziquantel (PZQ, 600 mg/kg orally), or both. Serum TNF-α, IL-17, IL-22, and IgE were quantified by ELISA. Hepatic STAT3 and β-catenin mRNA and let-7a miRNA expression were analyzed by quantitative RT-PCR, normalized to GAPDH and U6 snRNA, respectively, using the 2^(- ΔΔCt) method. Granuloma index and developmental phase distribution were assessed histologically.
resultsIL-22 treatment significantly reduced granuloma index (11.1% reduction, P < 0.05) and systemic TNF-α (16.8% reduction) and IgE (69.8% reduction), while inducing robust upregulation of hepatic STAT3 mRNA (10.4-fold, P < 0.05) and let-7a miRNA (10.6-fold, P < 0.05) with concomitant downregulation of β-catenin transcripts (48.9% reduction from infected levels, P < 0.05). In contrast, PZQ decreased inflammatory mediators and IgE but did not significantly reduce granuloma index and paradoxically increased β-catenin expression (60% elevation from infected levels, P < 0.05). Combination therapy additively suppressed TNF-α (63.8% reduction), IL-17 (35.2% reduction), and IgE (70.2% reduction).
conclusionIL-22 reshapes the hepatic molecular landscape by modulating the STAT3/β-catenin/let-7a signaling axis in S. mansoni-induced granulomas, providing a mechanistic basis for its use as an immunomodulatory adjunct to PZQ rather than as an alternative anthelmintic. These findings identify the STAT3/β-catenin/let-7a circuit as a molecular target for immunotherapeutic intervention in schistosomal hepatic pathology.
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