title: Imbalance between Th17 and regulatory T-cells in systemic lupus erythematosus.
abstract: Impaired function of regulatory T-cells (Treg) leads to a failure in immune tolerance and triggers autoimmunity. We analyzed whether the deficiency in Treg in systemic lupus erythematosus (SLE) is accompanied by an increase in effector T-cell responses. We studied the frequencies of IL-17A (Th17) and IFNg (Th1) producing CD4(+) T-cells by flow cytometric detection of intracellular cytokines in PMA/ionomycin stimulated blood lymphocytes from seven patients with active SLE, eight with SLE in remission, and 11 healthy controls. Circulating Treg were evaluated as CD4(+)CD25(+) lymphocytes expressing FoxP3. There was no difference in the percentage of Treg cells between the groups, but their absolute counts were decreased in active SLE (5 [1-7] cells/μL) compared to inactive SLE (11 [6-15]; p = 0.05) and healthy controls (16 [10-20]; p 〈 0.01). Both the frequency and numbers of Th1 cells were decreased in SLE compared to controls. No difference was observed in the number of Th17 cells, which resulted in a decreased Th1/Th17 ratio. In parallel, a higher Treg/Th17 ratio in healthy controls (2.2 [1.8-3.6]) compared to active SLE (1.1 [1.0-2.1]; p 〈 0.05) was observed. There was a correlation between the number of Treg cells and disease activity status (SLEDAI, r = -0.59). SLE patients in the active phase of the disease are characterized by a deficiency in Treg cells and decreased Treg/Th17 ratio. This suggests that the imbalance between major T-cells subsets might be responsible for an increased proinflammatory response in the exacerbation of SLE.
authors.affiliation: Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Weronika
authors.initials: W
authors.lastname: Kleczynska
authors.forename: Bogdan
authors.initials: B
authors.lastname: Jakiela
authors.forename: Hanna
authors.initials: H
authors.lastname: Plutecka
authors.forename: Mamert
authors.initials: M
authors.lastname: Milewski
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
authors.forename: Jacek
authors.initials: J
authors.lastname: Musial
mesh_terms: D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors