The TH17/Treg Imbalance in Rheumatoid Arthritis and Relation to Disease Activity

Abstract

Objectives: T regulatory cells (Treg) and proinflammatory T H 17 cells are newly identified T lymphocyte subsets, which have significant effects on autoimmunity and inflammation. Tregs play key role in the maintenance of selftolerance. T H 17/Treg disturbed balance has been reported to contribute to several autoimmune diseases. Our aim was to assess the Treg/T H 17 pattern and T H 17 related cytokines, in peripheral blood of Egyptian rheumatoid arthritis patients, and their relation to disease activity score (DAS). Analyzing IL17A and IL23 as indicators of T H 17 function, was to study the effect of T H 17 in RA. Methods: 100 Egyptian rheumatoid arthritis patients, divided into Group I (14), Group II (48), Group III (38), with low <3.2, moderate 3.2 to <5.1 and high >5.1, activity DAS score respectively; and 50 healthy age and sex matched controls were enrolled. Peripheral blood T H 17 and Treg (CD4 + CD25 + Foxp3 +) frequencies were analyzed by flowcytometry, and the serum levels of interleukins (IL17A), (IL23) were determined by ELISA. Results: Active RA patients (groups II and III) revealed an obvious increase in peripheral T H 17 frequencies, and levels of T H 17-related cytokines, and a significant decrease in Treg (CD4 + CD25 + Foxp3 +) frequencies in group III, when compared to healthy controls. T H 17/Treg ratios were positively correlated with serum concentrations of IL17A and IL23 cytokines. Frequencies and levels showed statistical significant correlation with DAS scoring. Conclusions: Our study indicated that T H 17/Treg balance was disturbed in peripheral blood of RA patients, leading to an increase of proinflammatory cytokines, correlating with DAS, and suggesting an important role in the development of RA.

Correlation of interleukin 6 and transforming growth factor β1 with peripheral blood regulatory T cells in rheumatoid arthritis patients: a potential biomarker

“…At first, flow cytometric results of RA patients revealed a significantly lower percentage of circulating CD4 + Foxp3 + CD25 high Tregs as compared to healthy controls. Similarly, our findings are consistent with most studies, although the authors have presented various conclusions [19-21]. A major differences between studies could be a result of the definition of Tregs in flow cytometric gating patterns [22-24].…”

Gallic acid regulates immune response in a mouse model of rheumatoid arthritis

“… 26 On the other hand, Treg cells suppress pro‐inflammatory responses by inhibiting the activation of T cell subsets including Th1 and Th17. 25 As expected, we observed that the populations of Th17 cells were elevated whereas the populations of Treg cells were reduced in the CIA mouse model. These characteristics are in agreement with the previous findings, where a shift in the Th17/Treg cell to the Th17 cell side leads to RA with more severe symptoms.…”

“…Both Th17 and Treg cells are known to have important roles in the RA, as supported by Th17/Treg imbalance observed in preclinical and clinical studies of RA 14,25 . Th17 cells are known to mediate bone destruction and promote joint inflammation in part by secreting IL‐17 26 .…”

“…Both Th17 and Treg cells are known to have important roles in the RA, as supported by Th17/Treg imbalance observed in preclinical and clinical studies of RA. 14 , 25 Th17 cells are known to mediate bone destruction and promote joint inflammation in part by secreting IL‐17. 26 On the other hand, Treg cells suppress pro‐inflammatory responses by inhibiting the activation of T cell subsets including Th1 and Th17.…”

Forkhead Box P3 (Foxp3) serum level and Foxp3 Gene-Promoter polymorphisms in Egyptian rheumatoid arthritis patients: A case-control study

“…who reported an elevated serum Foxp3 more in patients than control group (51% vs 18%, respectively). 17 Higher and lower mean Foxp3 levels were reported by Alzifzaf et al 19 and Gaafar et al 22 (16.9 and 1.01 ng/ml in patients with rheumatoid arthritis vs 26.4 and 1.72 ng/ml in control subjects, respectively).…”