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Activated type 17 helper T cells affect tofacitinib treatment outcomes
Yuki Ito1, Daisuke Watanabe2, Norihiro Okamoto1
1Division of Gastroenterology, Department of Internal Medicine, Kobe University Hospital, Kobe, Japan.
Scientific Reports
|February 19, 2025
Summary
High IL-17A cell infiltration in the colon predicts poor response to tofacitinib (TOF) treatment in ulcerative colitis (UC) patients. This finding aids in personalizing UC therapy by identifying non-responders early.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- Ulcerative colitis (UC) incidence is increasing globally, necessitating effective treatment strategies.
- Therapeutic options for UC, including biologics and Janus kinase (JAK) inhibitors like tofacitinib (TOF), have expanded.
- Predicting TOF treatment response in moderate to severe UC remains challenging.
Purpose of the Study:
- To investigate whether IL-17A-positive mononuclear cell infiltration in colonic mucosa predicts TOF treatment responsiveness in UC patients.
- To identify potential biomarkers for personalized TOF therapy.
Main Methods:
- Comparative analysis of UC patients treated with TOF, categorized into responder and failure groups.
- Immunohistochemical examination of colon biopsy samples to quantify IL-17A-positive cells.
- Re-analysis of existing RNA sequence datasets (GEO database).
Main Results:
- A significantly higher proportion of IL-17A-positive mononuclear cells was observed in the colonic mucosa of TOF treatment failure group compared to responders (38.2% vs. 21.2%).
- Re-analysis of RNA sequencing data suggested TOF impacts Th1 cells more than IL-17-producing Th17 cells.
Conclusions:
- Increased IL-17A-positive mononuclear cells in colonic mucosa may serve as a predictive biomarker for poor response to TOF treatment in UC.
- This finding supports the potential for personalized medicine approaches in UC management.
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