Decreased numbers of FoxP3-positive and TLR-2-positive cells in intestinal mucosa are associated with improvement in patients with active inflammatory bowel disease following selective leukocyte apheresis

Abstract

Impaired immunological tolerance to commensal enteric flora is considered one possible pathogenic mechanism of inflammatory bowel disease (IBD). Given that regulatory T cells and Toll-like receptor (TLR)-positive cells are key actors in mucosal immune regulation, we aimed to identify the dynamics of these actors in the intestinal mucosa in relation to clinical improvement following selective leukapheresis treatment. Ten patients with active IBD despite treatment with corticosteroids, immunomodulators, or anti-tumor necrosis factor therapy were assessed by immunohistochemical staining of colorectal mucosal biopsies obtained before and after five sessions (week 7) of granulocyte and monocyte adsorption apheresis (GCAP). The presence of FoxP3-positive regulatory T cells, macrophages, dendritic cells, and TLR-2 and-4 positive cells was determined in relation to short-(week 7) and long-term (week 52) clinical outcome data. Following GCAP, the number of FoxP3-(P = 0.012) and TLR-2 (P = 0.008)-positive cells significantly decreased in biopsies after 7 weeks, in parallel with both clinical improvement at week 7 and a longstanding response after 12 months. Downregulation of FoxP3 and TLR-2 cells in the colorectal mucosa mirrors both short-and long-term improvement in patients with active IBD responding to GCAP. This observation suggests a potential role of these cells in the pathogenesis of IBD and the induction of immunological tolerance in the mucosa.