Abstract
The objective of the study was to quantify the transcriptional profile, as the main T cell lineage-transcription factors on synovial fluid (SF) T cells, in relation to SF cytokines and T cell frequencies (%) of psoriatic arthritis (PsA) patients. Reverse phase protein array was employed to identify interleukin (IL)-23Rp19-, FOXP3- and related orphan receptor gamma T (RORγt)- protein and Janus associated tyrosine kinases 1 (JAK1), signal transducer and activator and transcription 1 (STAT1), STAT3 and STAT5 phosphoproteins in total T cell lysates from SF of PsA patients. IL-1β, IL-2, IL-6, IL-21 and interferon (INF)-γ were measured using a multiplex bead immunoassay in SF from PsA patients and peripheral blood (PB) from healthy controls (HC). Frequencies of CD4+CD25−, CD4+CD25high FOXP3+ and CD4+CD25high CD127low Treg, and either mean fluorescence intensity (MFI) of FOXP3+ on CD4+ Treg or MFI of classic IL-6 receptor (IL-6R) α expression on CD4+CD25− helper/effector T cells (Th/eff) and Treg cells, were quantified in SF of PsA patients and in PB from HC by flow cytometry (FC). In PsA SF samples, IL-2, IL-21 and IFN-γ were not detectable, whereas IL-6 and IL-1β levels were higher than in SF of non-inflammatory osteoarthritis patients. Higher levels of IL-23R-, FOXP3- and RORγt proteins and JAK1, STAT1, STAT3 and STAT5 were found in total T cells from SF of PsA patients compared with PB from HC. Direct correlations between JAK1 Y1022/Y1023 and STAT5 Y694, and STAT3 Y705 and IL6, were found in SF of PsA patients. Increased proportion of CD4+CD25high FOXP3+ and CD4+CD25high CD127low Treg cells and brighter MFI of IL-6Rα were observed both on CD4+CD25high- and CD4+CD25− T cells in PsA SF. The study showed a distinctive JAK1/STAT3/STAT5 transcriptional network on T cells in the joint microenvironment, outlining the interplay of IL-6, IL-23, IL-1β and γC cytokines in the polarization and plasticity of Th17 and Treg cells, which might participate in the perpetuation of joint inflammation in PsA patients.
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This work was supported by grants from the Italian Ministry of Education, University and Research (MIUR-2009EE3SWA; FIRB 2011).
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Fiocco, U., Martini, V., Accordi, B. et al. Transcriptional network profile on synovial fluid T cells in psoriatic arthritis. Clin Rheumatol 34, 1571–1580 (2015). https://doi.org/10.1007/s10067-015-3002-2
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DOI: https://doi.org/10.1007/s10067-015-3002-2