T2 enhances in situ level of Foxp3+ regulatory cells and modulates inflammatory cytokines in Crohn's disease.

BACKGROUND

Acting via IL-10 and transforming growth factor-β (TGF-β), t regulatory cells (Tregs) that express the Forkhead Box P3 (Foxp3) play a vital role in maintaining intestinal immune homeostasis. Many studies have found correlation between Foxp3(+) Treg cells and Crohn's disease (CD). T2, extracted from the medicinal plant Tripterygium wilfordii Hook F, has already been proved to be therapeutically effective in inducing the remission of CD. However, the mechanisms in human studies remain largely unknown.

OBJECTIVE

We aimed to explore the effect of T2 on the in situ levels of inflammatory cytokines and the number of Foxp3(+) Tregs in inflamed mucosa of CD.

METHODS

Mucosal biopsies from 20 patients treated with T2 were taken by colonoscopy. The changes of Foxp3(+) Tregs as well as TNF-α and IL-10 in diseased tissue were visualized by immunochemistry. Western blot and ELISA were used to quantify levels of Foxp3 protein expression and inflammatory cytokines.

RESULTS

T2 treatment ameliorated the pathological inflammation of CD. We observed that the significantly elevated Foxp3(+) Tregs and IL-10 levels in the mucosa of CD patients after T2 treatment concurred with the down-regulation of proinflammatory TNF-α.

CONCLUSIONS

We confirmed the efficacy of T2 treatment in CD and showed that microscopic inflammation was attenuated by the modulation of in situ levels of inflammatory cytokines. The therapeutic mechanisms might involve the up-regulation of Foxp3(+) Tregs.