Peripheral Blood from Rheumatoid Arthritis Patients Shows Decreased Treg CD25 Expression and Reduced Frequency of Effector Treg Subpopulation

Eunbyeol Go,Yeeun Kim,Su-Jin Yoo,Pureum Sun,Eui-Cheol Shin,Seong Wook Kang,Somin Kwon,Min Kyung Jung,Suyoung Choi,Bu Yeon Heo,Jinhyun Kim,Jaeyul Kwon,Ju-Gyeong Kang

doi:10.3390/cells10040801

Abstract

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by immune cell infiltration of the synovium, leading to the loss of cartilage, bone, and joint function. Although regulatory T (Treg) cells are thought to modulate the initiation and progression of RA, a consensus has yet to be reached regarding the function and composition of Treg cells in RA patients. To address these discrepancies, we analyzed not only the total Treg frequency but also that of Treg subpopulations in the peripheral blood of RA patients and healthy controls by flow cytometry. We found that the total Treg population was not significantly different between RA and control subjects. However, the effector Treg cell subgroup, defined as CD45RA−CD25hi, showed markedly decreased frequency in RA patients. In addition, the total Treg population from RA patients showed a significant decline in the expression of CD25. Both the naïve and effector Treg subgroups also showed marked reduction of CD25 expression in RA patients compared to controls. These data suggest that the decreased frequency of effector Treg cells and overall reduction of CD25 expression in Treg cells in the peripheral blood may be evidence of altered Treg homeostasis associated with RA pathogenesis.

Highlights

Given that abnormalities of IL-2/IL-2R signaling pathways may lead to the breakdown of self-tolerance mechanisms in Rheumatoid arthritis (RA), we examined whether expression of IL-2Rα (CD25) in Treg cells was altered in RA patients
We showed that despite using well-validated markers, the proportion of the total Treg cell population, such as CD25+ forkhead box P3 (Foxp3)+ and CD25+ Foxp3+ CD127−/low, in CD4+ T cells did not show any significant change in the peripheral blood of RA patients
Our analysis of Treg subgroups among CD4+ T cells and the total Treg population consistently demonstrated a significant reduction of effector Treg cells (CD25hi CD45RA− ) in RA patients

Summary

Introduction

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by the accumulation of inflammatory cells in the joints, leading to chronic synovitis, cartilage and creativecommons.org/licenses/by/ 4.0/). Bone damage, and eventual loss of joint function [1,2,3]. Forkhead box P3 (Foxp3)-positive regulatory T (Treg ) cells are responsible for maintaining immune tolerance and suppressing potentially harmful autoimmune responses [4]. Depletion of Treg cells has been shown to result in severe autoimmunity in animal models [5]. The subsequent release of pro-inflammatory cytokines such as TNF-α can further suppress Treg cell function and exacerbate symptoms [8,9]. The frequency and potential dysfunction of Treg cell in RA patients is highly controversial [6,10]

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Conclusion