The balance between Foxp3 and Ror-γt expression in peripheral blood is altered by tocilizumab and abatacept in patients with rheumatoid arthritis.

Yoshifumi Tada,Yoshinobu Nakao,Yukihide Ono,Nobuyuki Ono,Rie Suematsu,Syuichi Koarada,Satoko Tashiro,Yukiko Tokuda,Akihide Ohta,Yuri Sadanaga,Akihito Maruyama

doi:10.1186/s12891-016-1137-1

Abstract

BackgroundThe balance between Th17 cells and regulatory T (Treg) cells has been shown to play an important role in the development of rheumatoid arthritis (RA). Recent studies have shown that treatment with abatacept (ABT) or tocilizumab (TCZ) affects Th17 and Treg cell populations. Although not unanimously accepted, several reports have shown that Treg cells are decreased by ABT and increased by TCZ, and that Th17 cells are decreased by TCZ. To further investigate the effects of ABT and TCZ on the skewing of T cell populations, we analyzed the expression of master regulators genes of helper T cell lineages following ABT/TCZ treatment of RA patients.MethodsTen patients treated with ABT and 10 patients treated with TCZ were enrolled. Total RNA was extracted from peripheral blood cells at baseline, and after 12 and 24 weeks of therapy. The expression levels of T-bet, GATA3, Foxp3 and Ror-γt were semi-quantified using real-time PCR. The relative expression levels were expressed as the ratios of two genes (T-bet/GATA3, Foxp3/GATA3, Foxp3/T-bet, Foxp3/Ror-γt, Ror-γt/T-bet, Ror-γt/GATA3), and the changes in these ratios with treatment were determined.ResultsThe Foxp3/Ror-γt ratio was decreased after ABT therapy (0.67 ± 0.16 at 24 weeks, P = 0.0034) but was increased after TCZ therapy (2.00 ± 1.03 at 24 weeks, P = 0.0013). In addition, the Ror-γt/GATA3 ratio was decreased after TCZ therapy (0.78 ± 0.37 at 24 weeks, P = 0.0008). Except for these ratios, no significant skewing in the expression of these factors was detected. No significant relationship between clinical response to the treatment and change in the ratios of these factors was determined.ConclusionTreatment with TCZ or ABT differently affected the balance between Foxp3 and Ror-γt expression in the peripheral blood of patients with RA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1137-1) contains supplementary material, which is available to authorized users.

Highlights

The balance between Th17 cells and regulatory T (Treg) cells has been shown to play an important role in the development of rheumatoid arthritis (RA)
Recent studies reported the existence of forkhead box P3 (Foxp3)+ Regulatory T (Treg) cells that secrete IL-17 [25] and of Ror-γt + Th17 cells that differentiated from Foxp3+ Treg cells [26]
The mechanism of the decrease in the Treg cell population is not clear; our results suggest that the down-regulation of Foxp3 expression by ABT leads to a reduction in Treg cells

Summary

Introduction

The balance between Th17 cells and regulatory T (Treg) cells has been shown to play an important role in the development of rheumatoid arthritis (RA). Recent studies have shown that treatment with abatacept (ABT) or tocilizumab (TCZ) affects Th17 and Treg cell populations. Various recent studies have shown that the balance between Th17 cells and regulatory T (Treg) cells plays a critical role in the development of RA [4]. Potential defects in Treg-mediated tolerance have been proposed in RA [8] Based on these background findings, the changes in T cell subpopulations in patients with RA who were treated with ABT or TCZ have been investigated. These findings were not unanimous and conflicting results have been reported

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Discussion

Conclusion