Regulatory T Cells and IL-17A Levels in Noninfectious Uveitis

Graefes Arch Clin Exp Ophthalmol. 2020 Jun;258(6):1269-1278. doi: 10.1007/s00417-020-04649-0. Epub 2020 Mar 21.

Abstract

Purpose: Regulatory T cells (Tregs) have been intensively studied in a myriad of autoimmune diseases. As for noninfectious uveitis (NIU), results have been contradictory, and studies have failed to demonstrate a consistent reduction in Treg cell frequency in patients with active disease. The present study aims to characterize T lymphocyte subsets, including naïve and memory Tregs as well as their respective CD39 expression, in the peripheral blood of NIU patients. Inflammatory as well as suppressive cytokine profiles were also evaluated.

Methods: T cell subpopulations were evaluated by multiparametric flow cytometry using anti-CD3, anti-CD4, anti-CD45, anti-CD45RA, anti-CD197, anti-CD25, anti-CD127, and anti-CD39. Treg cells were defined as CD3 + CD4+CD25hiCD127low. A multiplex bead-based immunoassay was used to determine TNF-α, IFN-ɣ, IL-17A, IL-10, and TGF-β levels.

Results: Twenty-nine patients with active NIU were included as well as 15 sex- and age-matched controls. There were no significant differences in T lymphocyte subsets, including Tregs, between patients and controls. However, patients with a lower grade of anterior chamber or vitreous inflammatory cellular reaction showed higher memory Treg counts than controls, with no respective increase in CD39+ expression, and a tendency for higher IL-17A levels (p = 0.06). This IL-17A elevation was present in the total NIU group (p = 0.08) as well as a positive correlation between IL-17A levels and the absolute counts of memory Tregs (p = 0.013; R = 0.465). Patients with higher IL-17A levels also showed higher serum concentrations of memory (p = 0.001) and naïve (p = 0.003) Tregs as well as elevated TNF-α (p < 0.0001) and IFN-ɣ (p = 0.016) levels. Negative correlations were observed between IL-10 and TGF-β levels and the percentages of memory (p = 0.030; R = - 0.411) and total CD39+ Tregs (p = 0.051; R = - 0.373) in the peripheral blood of NIU patients.

Conclusion: Our results showed that total Treg levels were not reduced in patients with NIU. Further characterization of Treg subsets, including memory Tregs and respective CD39 expression, may provide additional insight on the role of Treg cells in NIU. Consistent high levels of circulating IL-17A in NIU patients are in accordance with previous studies and reinforce this cytokine's vital role in uveitis pathogenesis and its possible use as a therapeutic target.

Keywords: CD39; IL-17A; Memory Treg; Noninfectious uveitis; Regulatory T lymphocyte.