Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNFα treatment
Background and aims Inappropriate immune responses contribute to the continuous stimulation of the intestinal immune system in chronic inflammatory bowel disease (IBD). Among several pathogenic factors, a numerical deficiency of regulatory T (Treg) cells has been suggested to lead to an insufficient...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
1 April 2011
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| In: |
Gut
Year: 2011, Volume: 60, Issue: 10, Pages: 1345-1353 |
| ISSN: | 1468-3288 |
| DOI: | 10.1136/gut.2010.217117 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/gut.2010.217117 Verlag, lizenzpflichtig, Volltext: https://gut.bmj.com/content/60/10/1345 
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| Author Notes: | Claudia Veltkamp, Matthias Anstaett, Kristin Wahl, Sarah Möller, Saskia Gangl, Oliver Bachmann, Matthias Hardtke-Wolenski, Florian Länger, Wolfgang Stremmel, Michael P. Manns, Klaus Schulze-Osthoff, Heike Bantel |
| Summary: | Background and aims Inappropriate immune responses contribute to the continuous stimulation of the intestinal immune system in chronic inflammatory bowel disease (IBD). Among several pathogenic factors, a numerical deficiency of regulatory T (Treg) cells has been suggested to lead to an insufficient compensation of chronically activated T lymphocytes. This study was conducted to investigate whether increased apoptosis contributes to Treg cell deficiency in IBD and whether successful treatment with antitumour necrosis factor α (TNFα) is achieved by reducing of Treg cell apoptosis. - Methods Apoptosis of CD4+Foxp3+ Treg cells in tissue sections of patients with active IBD was analysed by immunohistochemistry and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) staining. Apoptosis of peripheral blood CD4+CD25+Foxp3+ Treg cells was investigated by flow cytometry and annexin-V staining. In addition, caspase activity and apoptosis were measured in sera of patients with IBD treated with anti-TNFα by a luminometric caspase enzyme assay. - Results It is demonstrated that patients with active IBD revealed increased apoptosis of local CD4+Foxp3+ Treg cells in the inflamed mucosa compared with non-inflamed control colon tissue. Moreover, in peripheral blood a reduced frequency and increased apoptosis of Treg cells were found and accompanied by elevated caspase activity in the serum. During anti-TNFα treatment, Treg cell apoptosis declined in close correlation with elevated peripheral Treg cell numbers and a decrease of caspase activation and disease activity. - Conclusions These data suggest that increased apoptosis of Treg cells plays a potentially important role in the pathogenesis of IBD and can be reversed by anti-TNFα treatment. Measurement of Treg cell apoptosis and serum caspase activity might therefore represent promising tools for monitoring disease activity and treatment response in patients with IBD. |
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| Item Description: | Gesehen am 07.12.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1468-3288 |
| DOI: | 10.1136/gut.2010.217117 |