Ustekinumab Improves Active Crohn's Disease by Suppressing the T Helper 17 Pathway

Yutaro Ihara, takehiro torisu, Kohta Miyawaki, Junji Umeno, Keisuke Kawasaki, Atsushi Hirano, Shin Fujioka, Yuta Fuyuno, Yuichi Matsuno, Takeshi Sugio, Kensuke Sasaki, Moriyama Tomohiko, Koichi Akashi, Takanari Kitazono

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalDigestion
DOIs
Publication statusAccepted/In press - 2021

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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