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Transcriptional network profile on synovial fluid T cells in psoriatic arthritis

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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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Acknowledgments

This work was supported by grants from the Italian Ministry of Education, University and Research (MIUR-2009EE3SWA; FIRB 2011).

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Authors and Affiliations

  1. Rheumatology Unit, Department of Medicine DIMED, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

    Ugo Fiocco, Francesco Caso, Luisa Costa, Francesca Oliviero, Anna Scanu, Mariele Gatto, Mara Felicetti, Paola Frallonardo, Roberta Ramonda, Lucia Piva, Leonardo Punzi & Andrea Doria

  2. Haematology and Clinical Immunology Branch, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

    Veronica Martini, Monica Facco, Daniele Boso, Renato Zambello, Carlo Agostini & Gianpietro Semenzato

  3. Department of Woman and Child Health, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

    Benedetta Accordi & Giuseppe Basso

  4. Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, via S. Pansini 5, 80131, Naples, Italy

    Francesco Caso, Luisa Costa & Raffaele Scarpa

  5. Faculty of Medicine, CMU, CH-1211, Geneva, Switzerland

    Jean-Michel Dayer

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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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