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Supplementary Material for: Ustekinumab Improves Active Crohn’s Disease by Suppressing the T Helper 17 Pathway

posted on 22.07.2021, 04:08 by Ihara Y., Torisu T., Miyawaki K., Umeno J., Kawasaki K., Hirano A., Fujioka S., Fuyuno Y., Matsuno Y., Sugio T., Sasaki K., Moriyama T., Akashi K., Kitazono T.
Background: Ustekinumab (UST), an antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, is effective in treating Crohn’s disease (CD). To clarify the mechanism of UST, we investigated T-cell differentiation in CD patients treated with UST. Methods: Twenty-seven patients with active CD were enrolled in this study. Seventeen patients were treated with UST, and 10 patients were treated with anti-tumor necrosis factor (TNF)-alpha therapy. The changes in the proportions of T-cell subsets after these therapies were analyzed by flow cytometry. Comprehensive gene expression changes in the colonic mucosa were also evaluated. Results: The frequency of T helper (Th) 17 cells was significantly decreased in the peripheral blood of patients with active CD after UST therapy. Anti-TNF therapy had a minimal effect on Th17 cells but increased the proportion of regulatory T cells. Enrichment analysis showed the expression of genes involved in the Th17 differentiation pathway was downregulated in the colonic mucosa after UST but not anti-TNF therapy. There were no common differentially expressed genes between CD patients treated with UST and anti-TNF therapy, suggesting a clear difference in their mechanism of action. Conclusion: In patients with active CD, UST therapy suppressed Th17 cell differentiation both in the peripheral blood and colonic tissues.