Ustekinumab Decreases Circulating Th17 Cells in Ulcerative Colitis

Area of Science:

• Immunology
• Gastroenterology
• Pharmacology

Background:

• T helper (Th) cells are implicated in ulcerative colitis (UC) pathogenesis.
• Ustekinumab (UST), an interleukin-12/23p40 antibody, is used for UC treatment.
• Understanding UST's immunomodulatory effects on T cells in UC is crucial.

Purpose of the Study:

• To analyze circulating T cell subset alterations following ustekinumab (UST) administration in patients with ulcerative colitis (UC).
• To correlate changes in T cell populations with clinical and serological improvements in UC patients treated with UST.

Main Methods:

• CD4 T cells were isolated from peripheral blood of 13 UC patients before and after 8 weeks of UST treatment.
• Flow cytometry was used to analyze the proportions of T helper cell subsets (Th1, Th2, Th17, regulatory T cells).
• Clinical data (partial Mayo score) and laboratory parameters were assessed at 0, 8, and 16 weeks.

Main Results:

• Ustekinumab treatment led to significant clinical improvement in UC patients, with a decrease in partial Mayo score (median 4 to 0, p<0.001).
• Serological markers including albumin, C-reactive protein, and sedimentation rate improved significantly.
• A significant reduction in Th17 cells (1.85% to 0.98%, p<0.0001) and an increase in Th1 cells (9.52% to 10.4%, p<0.05) were observed. No significant changes in Th2 or regulatory T cells.
• Patients with lower Th17 cell levels at baseline showed better clinical outcomes at 16 weeks.

Conclusions:

• Ustekinumab treatment effectively reduces circulating Th17 cells in ulcerative colitis patients.
• The decrease in Th17 cells is strongly associated with the anti-inflammatory effects and clinical remission achieved with UST therapy.
• Targeting Th17 cells represents a potential therapeutic strategy for managing ulcerative colitis.