Late Crohn's disease patients present an increase in peripheral Th17 cells and cytokine production compared with early patients

Abstract

[Background]: Th1 and Th17 cells have been implicated in Crohn's disease (CD) pathophysiology and may play a role in disease persistence. [Aim]: To determine Th1 and Th17 responses in intestine and peripheral blood of early (<32 weeks since initial symptoms) and late (>2 years) CD patients. [Methods]: Cytokine mRNA in intestinal biopsies was determined by RT-PCR. Cytokine concentration in culture was measured by ELISA and cytokine-producing cells were identified by intracellular staining. [Results]: The inflamed mucosa showed significantly increased IL-17 mRNA levels compared with non-inflamed areas, both in early and late CD patients. However, only patients with late (n = 12), but not early (n = 9), active disease showed increased IL-17 production, as well as a significantly higher percentage of IL-17+CD4+ cells in blood, compared with controls (n = 12) or patients in remission (n = 13). Moreover, cultured peripheral CD4 + cells from late active CD patients presented significantly higher percentages of IL-17+, IL-22+ and IFN-γ+ and a significantly increased production of IL-17 and IL-22, but not IFN-γ+. [Conclusions]: Increased IL-17 gene transcription is common to early and late CD mucosa. However, exacerbated Th17 responses in the peripheral blood appear only in late disease. We propose that this population may constitute a mechanism of perpetuating the disease. © 2010 Blackwell Publishing Ltd.