Reciprocal changes of Foxp3 expression in blood and intestinal mucosa in IBD patients responding to infliximab† (original) (raw)
Journal Article
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1Laboratory of Experimental Immunology, Catholic University of Leuven, Leuven, Belgium
2Division of Gastroenterology, Catholic University of Leuven, Leuven, Belgium
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2Division of Gastroenterology, Catholic University of Leuven, Leuven, Belgium
3Department of Molecular Cell Biology, Catholic University of Leuven, Leuven, Belgium
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4Morphology and Molecular Pathology Section, Catholic University of Leuven, Leuven, Belgium
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Séverine Vermeire, MD, PhD
2Division of Gastroenterology, Catholic University of Leuven, Leuven, Belgium
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2Division of Gastroenterology, Catholic University of Leuven, Leuven, Belgium
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Dominique Bullens, MD, PhD
1Laboratory of Experimental Immunology, Catholic University of Leuven, Leuven, Belgium
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1Laboratory of Experimental Immunology, Catholic University of Leuven, Leuven, Belgium
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4Morphology and Molecular Pathology Section, Catholic University of Leuven, Leuven, Belgium
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3Department of Molecular Cell Biology, Catholic University of Leuven, Leuven, Belgium
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2Division of Gastroenterology, Catholic University of Leuven, Leuven, Belgium
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Received:
15 December 2009
Accepted:
23 December 2009
Cite
Zhe Li, Ingrid Arijs, Gert De Hertogh, Séverine Vermeire, Maja Noman, Dominique Bullens, Lieve Coorevits, Xavier Sagaert, Frans Schuit, Paul Rutgeerts, Jan L. Ceuppens, Gert Van Assche, Reciprocal changes of Foxp3 expression in blood and intestinal mucosa in IBD patients responding to infliximab†, Inflammatory Bowel Diseases, Volume 16, Issue 8, 1 August 2010, Pages 1299–1310, https://doi.org/10.1002/ibd.21229
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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. Inflamm Bowel Dis 2010
Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.
Topic:
- inflammatory bowel disease
- intestinal mucosa
- t-lymphocytes
- mucous membrane
- irritable bowel syndrome
- infliximab
- antigens, cd25
- regulatory t-lymphocytes
- foxp3 gene
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