Atorvastatin upregulates regulatory T cells and reduces clinical disease activity in patients with rheumatoid arthritis

Yu-Hua Liao,Rui Yao,Ying-Jun Ding,Ting-Ting Tang,Zi-Hua Zhou,Harish Jevallee,Meng-Yang Liao,Hong Xiao,You Song,Xian Yu,Xiang Cheng,Guo-Ping Shi,Jing Yuan,Rong Du

doi:10.1194/jlr.m010876

Abstract

In this study, we investigated the hypothesis that regulatory T cells (T(reg)) are involved in the immunomodulatory effects of statins on rheumatoid arthritis (RA) patients. The 12-week study cohort consisted of 55 RA patients and 42 control subjects allocated to either a group treated with atorvastatin (AT) (20 mg/day) or a non-AT group. T(reg) numbers, suppressive function, serum inflammatory markers, and disease activity were evaluated before and after the therapy. Furthermore, the effects of AT on the frequency and suppressive function of T(reg) were determined in vitro. Our data revealed that the suppressive function of T(reg) from RA patients significantly decreased compared with that of control subjects. AT significantly reduced erythrosedimentation, C-reactive protein, and disease activity. Concomitantly, T(reg) numbers and suppressive functions were significantly improved by AT. Consistent with the in vivo experiments, AT promoted the generation of T(reg) from primary T cells and enhanced preexisting T(reg) function in vitro. Moreover, we showed that PI3K-Akt-mTOR and ERK signal pathways were involved in the induction of T(reg) by AT. In conclusion, AT significantly increased T(reg) numbers and restored their suppressive function in the RA patients, and this may be relevant in the modulation of uncontrolled inflammation in this disorder.

Highlights

In this study, we investigated the hypothesis that regulatory T cells (Treg) are involved in the immunomodulatory effects of statins on rheumatoid arthritis (RA) patients
The peripheral blood mononuclear cell (PBMC) of RA patients (n = 55) and control (n = 42) donors were stained with fluorescent-labeled antibodies against CD4, CD25, and Foxp3
It is possible that Treg are involved in the physiopathogenesis of rheumatoid arthritis

Summary

Introduction

We investigated the hypothesis that regulatory T cells (Treg) are involved in the immunomodulatory effects of statins on rheumatoid arthritis (RA) patients. Suppressive function, serum inflammatory markers, and disease activity were evaluated before and after the therapy. Our data revealed that the suppressive function of Treg from RA patients significantly decreased compared with that of control subjects. AT significantly increased Treg numbers and restored their suppressive function in the RA patients, and this may be relevant in the modulation of uncontrolled inflammation in this disorder.—Tang, T-T., Y. Atorvastatin upregulates regulatory T cells and reduces clinical disease activity in patients with rheumatoid arthritis. A downregulation of CD127 has been shown to be closely correlated with Foxp3 [3] It can be used as a reliable surface marker for Treg. A number of studies have shown that statin treatment benefits RA patients, which

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Conclusion