Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNFα treatment

• Verfasst von: Veltkamp, Claudia [VerfasserIn]
• Verfasst von: Anstaett, Matthias [VerfasserIn]
• Verfasst von: Wahl, Kristin [VerfasserIn]
• Verfasst von: Möller, Sarah [VerfasserIn]
• Verfasst von: Gangl, Saskia [VerfasserIn]
• Verfasst von: Bachmann, Oliver [VerfasserIn]
• Verfasst von: Hardtke-Wolenski, Matthias [VerfasserIn]
• Verfasst von: Länger, Florian [VerfasserIn]
• Verfasst von: Stremmel, Wolfgang [VerfasserIn]
• Verfasst von: Manns, Michael P. [VerfasserIn]
• Verfasst von: Schulze-Osthoff, Klaus [VerfasserIn]
• Verfasst von: Bantel, Heike [VerfasserIn]
• Titel: Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNFα treatment
• Verf.angabe: 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
• E-Jahr: 2011
• Jahr: 1 April 2011
• Umfang: 9 S.
• Fussnoten: Gesehen am 07.12.2022
• Titel Quelle: Enthalten in: Gut
• Ort Quelle: London : BMJ Publishing Group, 1960
• Jahr Quelle: 2011
• Band/Heft Quelle: 60(2011), 10, Seite 1345-1353
• ISSN Quelle: 1468-3288
• DOI: doi:10.1136/gut.2010.217117
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: anti-TNFα
• Sach-SW: Apoptosis
• Sach-SW: caspases
• Sach-SW: inflammatory bowel disease
• Sach-SW: Treg cells
• K10plus-PPN: 1826462562

Abstract

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.