Association of Increased Treg Cell Levels With Elevated Indoleamine 2,3-Dioxygenase Activity and an Imbalanced Kynurenine Pathway in Interferon-Positive Primary Sjogren's Syndrome

Autor: Maria, NI, Van Helden - Meeuwsen, Corine, Brkic, Zana, Paulissen, Sandra, Steenwijk, Eline, Dalm, V.A.S.H., van Daele, Paul, van Hagen, P.M., Kroese, FGM, van Roon, JAG, Harkin, A, Dik, Wim, Drexhage, Hemmo, Lubberts, Erik, Versnel, Marjan
Přispěvatelé: Immunology, Pharmacy, Rheumatology, Internal Medicine
Rok vydání: 2016
Zdroj: ARTHRITIS & RHEUMATOLOGY, 68(7), 1688-1699. John Wiley & Sons Ltd.
ISSN: 2326-5191
Popis: Objective. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme that converts tryptophan to kynurenine, is driven in part by type I and type II interferons (IFNs). Naive T cells are polarized into FoxP31 Treg cells upon exposure to either IDO1cells or kynurenine. Recent studies have suggested that the kynurenine pathway reflects a crucial interface between the immune and nervous system. The aims of the present study were to evaluate whether Treg cell levels are elevated, in conjunction with increased IDO activity, in patients with primary Sjogren's syndrome (SS) who are positive for the IFN gene expression signature, and to investigate the downstream kynurenine pathway in these patients. Methods. Serum from 71 healthy controls, 58 IFN-negative patients with primary SS, and 66 IFN-positive patients with primary SS was analyzed using high-performance liquid chromatography to measure the levels of tryptophan and kynurenine. Expression levels of messenger RNA (mRNA) for IDO and downstream enzymes in the kynurenine pathway were assessed in CD141 monocytes using real-time quantitative polymerase chain reaction. CD4+CD45RO+ T helper memory cell populations were analyzed by flow cytometry. Results. Significantly increased levels of IDO activity (assessed as the kynurenine: tryptophan ratio) (P=0.0054) and percentages of CD25 high FoxP31 Treg cells (P=0.039) were observed in the serum from IFN-positive patients with primary SS, and these parameters were significantly correlated with one another (r=0.511, P=0.002). In circulating monocytes from IFN-positive patients with primary SS, the expression of IDO1 mRNA was up-regulated (P
Databáze: OpenAIRE
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