Indoleamine 2,3-dioxygenase-expressing peripheral cells in rheumatoid arthritis and systemic lupus erythematosus: a cross-sectional study

Abstract

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme which suppresses T lymphocyte activity and induces Foxp3+ CD4+ regulatory T cells (Tregs) polarisation. The aim of this study was to evaluate the expression of IDO in freshly isolated peripheral cells as well as to enumerate Tregs and Th17 subpopulation in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. The percentage of IDO-expressing cells as well as Tregs and Th17 was evaluated in 14 active RA- (aRA), 13 inactive RA- (iRA), 7 aSLE-, 12 iSLE-treated patients and 11 healthy donors (controls). Intracellular IDO was analysed by flow cytometry in CD14+, CD8α+, CD16+ and CD123+ cell subpopulations. Tregs and Th17 were assessed by intracellular of Foxp3 and IL17A detection in CD4+ CD14- cells. A total of 50,000 events were recorded for each sample. The amounts of CD14+/CD16-/IDO+, CD14-/CD16+/IDO+ and CD14+/CD16+/IDO+-expressing peripheral cells were slightly lower in inactive vs. active disease in RA and SLE patients. Notwithstanding, only inactive patients had statistically significant lower percentages when compared to controls. aRA and iRA showed a statistically significant decrease in CD8α+/CD123+/IDO+ vs. controls. Meanwhile, only iSLE patients had lower CD8α+/CD123+/IDO+ cells vs. aSLE patients and controls. Th17 subset was present in higher amounts in aRA and iRA patients vs. controls. Tregs showed an increase in aRA patients vs. controls. A decreased percentage of IDO-expressing peripheral cells were determined in iRA and iSLE compared to controls. It could play a critical role in tolerance loss in these diseases.