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

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)

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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