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Title: Reciprocal changes of Foxp3 expression in blood and intestinal mucosa in IBD patients responding to infliximab
Authors: Li, Zhe ×
Arijs, Ingrid
De Hertogh, Gert
Vermeire, Severine
Noman, Maja
Bullens, Dominique
Coorevits, Godelieve
Sagaert, Xavier
Schuit, Frans
Rutgeerts, Paul
Ceuppens, Jan
Van Assche, Gert #
Issue Date: Aug-2010
Publisher: John Wiley & Sons
Series Title: Inflammatory Bowel Diseases vol:16 issue:8 pages:1299-1310
Abstract: 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.
URI: 
ISSN: 1078-0998
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Pediatric Immunology
Translational Research in GastroIntestinal Disorders
Translational Cell & Tissue Research
Gene Expression Unit
Laboratory of Clinical Immunology
× corresponding author
# (joint) last author

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