Abstract
The T-helper 17 (Th17) cells have a prominent role in inflammation as well as in bone and join destruction in both rheumatoid and psoriatic arthritis (RA and PsA). Here, we studied Th17 cell differentiation in RA and PsA. Blood samples from healthy donors, RA and PsA patients were collected. CD45RO- (naive) and CD45RO+ (memory) T cells were isolated from peripherial blood mononuclear cell by magnetic separation. Naive T cells were stimulated with anti-CD3, anti-CD28, and goat anti-mouse IgG antibodies and treated with transforming grow factor beta, interleukin (IL)-6, IL-1β, and IL-23 cytokines and also with anti-IL-4 antibody. IL-17A and IL-22 production were measured by enzyme linked immunosorbent assay, RORC, and T-box 21 (TBX21) expression were analyzed by quantitative polymerase chain reaction and flow cytometry. C-C chemokine receptor 6 (CCR6), CCR4, and C-X-C motif chemokine receptor 3 expression were determined by flow cytometry. Cell viability was monitored by impedance-based cell analyzer (CASY-TT). RORC, TBX21, CCR6, and CCR4 expression of memory T cells of healthy individuals (but not RA or PsA patients) were increased (p < 0.01; p < 0.001; p < 0.05; p < 0.05, respectively) compared to the naive cells. Cytokine-induced IL-17A production was different in both RA and PsA patients when compared to healthy donors (p = 0.0000026 and p = 0.0001047, respectively). By contrast, significant differences in IL-22 production were observed only between RA versus healthy or RA versus PsA patients (p = 0.000006; p = 0.0013454, respectively), but not between healthy donors versus PsA patients. The naive CD4 T-lymphocytes are predisposed to differentiate into Th17 cells and the in vitro Th17 cell differentiation is profoundly altered in both RA and PsA.
Highlights
T-helper 17 (Th17) cells are the third major subpopulation in addition to Th1 and Th2, which was described in mice [1] and in human [2]
The CD4+CD45RO+ and CD4+ CD45RO− cells were isolated from healthy donors, rheumatoid arthritis (RA), and psoriatic arthritis (PsA) patients and Th17- and Th1-specific transcription factors were measured by quantitative real-time PCR
Numerous observations were published regarding the serum IL-17A levels and the frequency of Th17 cells, these data do not reflect the potential plasticity of the circulating naive T cells
Summary
T-helper 17 (Th17) cells are the third major subpopulation in addition to Th1 and Th2, which was described in mice [1] and in human [2]. Th17 cells are necessary for the physiological defense against extracellular bacterial and fungal infections They contribute to inflammation in several autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis, inflammatory bowel diseases, psoriasis, or psoriatic arthritis (PsA) [3,4,5,6,7,8]. The Th17-derived cytokines induce the production of nume rous inflammatory mediator and effector molecules, such as proinflammatory cytokines IL-6 and IL-1β, nitric oxide, matrix metalloproteinases, granulocyte-monocyte colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) This complex effect includes neutrophil recruitment, osteoclastogenesis, synovial proliferation, and may lead to bone and joint destruction in RA [3,4,5, 7, 9,10,11,12]. We studied Th17 cell differentiation in RA and PsA
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