Ustekinumab Improves Active Crohn's Disease by Suppressing the T Helper 17 Pathway.
Adalimumab
Comprehensive gene expression analysis
Flow cytometry
Infliximab
Ustekinumab
Journal
Digestion
ISSN: 1421-9867
Titre abrégé: Digestion
Pays: Switzerland
ID NLM: 0150472
Informations de publication
Date de publication:
2021
2021
Historique:
received:
26
03
2021
accepted:
10
06
2021
pubmed:
6
8
2021
medline:
6
11
2021
entrez:
5
8
2021
Statut:
ppublish
Résumé
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. 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. 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. In patients with active CD, UST therapy suppressed Th17 cell differentiation both in the peripheral blood and colonic tissues.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
In patients with active CD, UST therapy suppressed Th17 cell differentiation both in the peripheral blood and colonic tissues.
Identifiants
pubmed: 34350861
pii: 000518103
doi: 10.1159/000518103
doi:
Substances chimiques
Tumor Necrosis Factor Inhibitors
0
Ustekinumab
FU77B4U5Z0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
946-955Informations de copyright
© 2021 S. Karger AG, Basel.