Reciprocal changes of Foxp3 expression in blood and intestinal mucosa in IBD patients responding to infliximab

Inflamm Bowel Dis. 2010 Aug;16(8):1299-310. doi: 10.1002/ibd.21229.


Background: Immune therapies may act in inflammatory bowel diseases (IBD) by modulating regulatory T cells (Tregs). Therefore, we investigated the effect of infliximab (IFX) therapy on Forkhead box protein3 (Foxp3) T cells in blood and intestinal mucosa from Crohn's disease (CD) and ulcerative colitis (UC).

Methods: Forty patients with active IBD (23 CD / 17 UC) were treated with IFX 5 mg/kg intravenously at weeks 0, 2, 6, and each 8 weeks thereafter. Blood samples were obtained before every infusion and T-lymphocyte subsets were characterized by flow cytometry. Foxp3 expression in intestinal biopsies from 43 patients with active IBD (19 CD / 24 UC) before and after IFX infusion and from 6 controls were assessed by quantitative reverse-transcription polymerase chain reaction and immunohistochemistry. Plasma C-reactive protein (CRP), clinical response, and endoscopic healing data were collected in parallel.

Results: IFX therapy resulted in a significant and sustained relative increase of CD4(+)CD25(+)Foxp3(+) Treg and of CD4(+)CD25(-)Foxp3(+) Treg cells in peripheral blood (both P < 0.0001 compared to baseline), particularly in responders (both P < 0.05 compared to nonresponders). The change in CRP over time inversely correlated with the increase of CD25(+)Foxp3(+) cells (P < 0.001, r = -0.39) and durable clinical response was associated with a sustained increase of circulating Foxp3(+) cells. Surprisingly, IFX therapy downregulated mucosal mRNA and protein expression of Foxp3 in UC and CD responders (both P < 0.001) but not in nonresponders.

Conclusions: IFX therapy has opposite effects in Foxp3(+) Treg cells in blood and gut mucosa, which suggests a redistribution of this important T-cell subset.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • C-Reactive Protein / analysis
  • Endoscopy
  • Female
  • Forkhead Transcription Factors / biosynthesis*
  • Forkhead Transcription Factors / blood*
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / immunology
  • Infliximab
  • Intestinal Mucosa / immunology*
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology*


  • Antibodies, Monoclonal
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Gastrointestinal Agents
  • C-Reactive Protein
  • Infliximab