Ustekinumab Improves Active Crohn's Disease by Suppressing the T Helper 17 Pathway.
Digestion
; 102(6): 946-955, 2021.
Article
en En
| MEDLINE
| ID: mdl-34350861
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Crohn
/
Ustekinumab
Límite:
Humans
Idioma:
En
Revista:
Digestion
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón