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Anti tumour necrosis-? therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn's disease

Anti tumour necrosis-? therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn's disease
Anti tumour necrosis-? therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn's disease
Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Its pathogenesis is not completely understood, though the prevailing model is that the intestinal flora drives a strong intestinal T helper 1 (Th1)/Th17 type immune response and inflammation in the genetically susceptible host. This leads to overly aggressive T-cell responses to normal bacteria causing tissue damage. Intestinal homeostasis and maintenance of tolerance to harmless antigens in the intestine has been shown to be maintained by CD4+ CD25+ T regulatory cells (Treg) in animal models of inflammatory bowel diseases. Here we investigated whether Infliximab, a chimeric monoclonal antibody directed against tumour necrosis factor (TNF)-alpha shown to be highly effective in the treatment of CD, has any effect on mucosal CD4+ CD25+ (FOXP3+) Tregs. Colonic mucosal biopsies from children with active Crohn's disease treated in vivo with Infliximab and controls were analysed to determine FOXP3 expression by immunofluorescence and reverse transcription-polymerase chain reaction. We observed that FOXP3+ T cells were significantly reduced in mucosa of CD patients with active disease compared with controls and restored to normal following Infliximab treatment. The frequency of FOXP3+ cells and mRNA expression was significantly increased in CD mucosa from patients treated in vivo with Infliximab compared with CD patients treated with conventional therapies. In conclusion, we show that Infliximab treatment does not solely neutralize soluble TNF-alpha, but also affects activation and possibly expansion of mucosal regulatory T cells. We suggest that anti TNF-alpha immunotherapy can also restore mucosal homeostasis in Crohn's disease
anti-tnf-? therapy, crohn's disease, foxp3, inflammation, regulatory t cells
0019-2805
178-183
Ricciardelli, Ida
96d57da0-8912-42aa-8610-c31a15e981a1
Lindley, Keith J.
6a886be5-733d-4c21-b9e4-f7ca61036ed6
Londei, Marco
8e3daa14-6b85-45b8-bac9-c93b05483434
Quaratino, Sonia
a17d78fe-6c03-4775-83e3-53f9d511ae70
Ricciardelli, Ida
96d57da0-8912-42aa-8610-c31a15e981a1
Lindley, Keith J.
6a886be5-733d-4c21-b9e4-f7ca61036ed6
Londei, Marco
8e3daa14-6b85-45b8-bac9-c93b05483434
Quaratino, Sonia
a17d78fe-6c03-4775-83e3-53f9d511ae70

Ricciardelli, Ida, Lindley, Keith J., Londei, Marco and Quaratino, Sonia (2008) Anti tumour necrosis-? therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn's disease. Immunology, 125 (2), 178-183. (doi:10.1111/j.1365-2567.2008.02839.x). (PMID:18422560)

Record type: Article

Abstract

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Its pathogenesis is not completely understood, though the prevailing model is that the intestinal flora drives a strong intestinal T helper 1 (Th1)/Th17 type immune response and inflammation in the genetically susceptible host. This leads to overly aggressive T-cell responses to normal bacteria causing tissue damage. Intestinal homeostasis and maintenance of tolerance to harmless antigens in the intestine has been shown to be maintained by CD4+ CD25+ T regulatory cells (Treg) in animal models of inflammatory bowel diseases. Here we investigated whether Infliximab, a chimeric monoclonal antibody directed against tumour necrosis factor (TNF)-alpha shown to be highly effective in the treatment of CD, has any effect on mucosal CD4+ CD25+ (FOXP3+) Tregs. Colonic mucosal biopsies from children with active Crohn's disease treated in vivo with Infliximab and controls were analysed to determine FOXP3 expression by immunofluorescence and reverse transcription-polymerase chain reaction. We observed that FOXP3+ T cells were significantly reduced in mucosa of CD patients with active disease compared with controls and restored to normal following Infliximab treatment. The frequency of FOXP3+ cells and mRNA expression was significantly increased in CD mucosa from patients treated in vivo with Infliximab compared with CD patients treated with conventional therapies. In conclusion, we show that Infliximab treatment does not solely neutralize soluble TNF-alpha, but also affects activation and possibly expansion of mucosal regulatory T cells. We suggest that anti TNF-alpha immunotherapy can also restore mucosal homeostasis in Crohn's disease

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More information

Published date: October 2008
Keywords: anti-tnf-? therapy, crohn's disease, foxp3, inflammation, regulatory t cells

Identifiers

Local EPrints ID: 79352
URI: http://eprints.soton.ac.uk/id/eprint/79352
ISSN: 0019-2805
PURE UUID: 919026eb-c3cb-4dc5-9d5a-6956b526687e

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Date deposited: 15 Mar 2010
Last modified: 14 Mar 2024 00:29

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Contributors

Author: Ida Ricciardelli
Author: Keith J. Lindley
Author: Marco Londei
Author: Sonia Quaratino

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