Indoleamine 2,3-dioxygenase-expressing peripheral cells in rheumatoid arthritis and systemic lupus erythematosus: a cross-sectional study Janette Furuzawa-Carballeda, Guadalupe Lima, Juan Jakez-Ocampo and Luis Llorente Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Me ´ dicas y Nutricio ´ n Salvador Zubira ´ n, Vasco de Quiroga No. 15, Col Seccio ´ n XVI, CP 14000, Mexico City, Mexico ABSTRACT Background 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. Materials and methods 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+, CD8a+, 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. Results 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 CD8a+ ⁄ CD123+ ⁄ IDO+ vs. controls. Meanwhile, only iSLE patients had lower CD8a+ ⁄ 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. Conclusions 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. Keywords CD8a ⁄ CD123 ⁄ IDO cells, indoleamine 2,3-dioxygenase, rheumatoid arthritis, systemic lupus erythematosus, Th17, Tregs. Eur J Clin Invest 2011; 41 (10): 1037–1046 Introduction Progress in elucidating cellular, molecular and biochemical processes that regulate immune response provides increas- ingly plausible explanations for the normal status of tolerance to self antigens that guards most humans from Ehrlich’s imagined horror autotoxicus [1]. Emerging data on regulatory antigen presenting cells provide fertile ground for resolving some perplexing immunological paradoxes. One specific mechanism that appears to play a key role is the catabolism of the essential aminoacid tryptophan, by the enzyme indoleamine-pyrrole 2,3-dioxygenase (EC 1Æ13Æ11Æ42), also known as indoleamine 2,3-dioxygenase or IDO [2,3]. Although at first sight, tryptophan catabolism is not involved in immune responses to specific stimuli, there is a growing body of experimental evidence that points towards the relevance of this biochemical process in immunoregula- tion [4–6]. IDO is expressed in various human cells such as endothelial cells and activated macrophages, plasmacytoid dendritic cells (pDC), myeloid (mDC) or conventional monocyte-derived DC (cDC) as well as Langerhans cells. IDO is up-regulated during antigen presentation by the engagement of CTLA-4 ⁄ B7Æ1 ⁄ B7Æ2 (CD80 ⁄ CD86) molecules on lymphocytes and human DCs, in response to infection (ligation of lipopolysaccharides and nucleic acids to toll-like receptor [TLR] 4 and TLR9, European Journal of Clinical Investigation Vol 41 1037 DOI: 10.1111/j.1365-2362.2011.02491.x ORIGINAL ARTICLE