Fenofibrate enhances the in vitro differentiation of Foxp3 + regulatory T cells in mice

Foxp3 + regulatory t cells (tregs) play a critical role in maintaining immune self-tolerance. reduced number and activity of tregs are usually found in autoimmune and inflammatory diseases,and enhancing the differentiation of tregs may be a promising therapeutic strategy. some reports suggested an anti-inflammatory and anti-autoimmune potential for fenofibrate,a hypolipidemic drug used worldwide,whose lipid effects are mediated by the activation of peroxisome proliferator-activated receptor α (pparα). in the present paper,we found that fenofibrate dose-dependently increased transforming growth factor-β and interleukin-2-induced treg differentiation in vitro,by 1.96-fold from 0 to 20 μm (12.59 ± 1.34 to 24.69 ± 3.03,p < 0.05). other ppar activators,wy14643 (100 μm),gemfibrozil (50 μm),and bezafibrate (30 μm),could not enhance treg differentiation. in addition,ppar could not upregulate the promoter activity of the treg-specific transcription factor foxp3. fenofibrate might exert its function by enhancing smad3 phosphorylation,a critical signal in treg differentiation,via akt suppression. our work reveals a new ppar independent anti-inflammatory mechanism of fenofibrate in up-regulating mouse treg differentiation. copyright 2012 zhou zhou et al.