Transcriptional network profile on synovial fluid T cells in psoriatic arthritis

作者: Ugo Fiocco , Veronica Martini , Benedetta Accordi , Francesco Caso , Luisa Costa

DOI: 10.1007/S10067-015-3002-2

关键词: Cancer researchMedicineT cellFOXP3RAR-related orphan receptor gammaSynovial fluidInterferonInterleukin 6Flow cytometryInterleukin

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

参考文章(57)
B F Leeb, H Bröll, G Partsch, A Dunky, J S Smolen, G Steiner, Highly increased levels of tumor necrosis factor-alpha and other proinflammatory cytokines in psoriatic arthritis synovial fluid The Journal of Rheumatology. ,vol. 24, pp. 518- 523 ,(1997)
H Zola, L Flego, Expression of interleukin-6 receptor on blood lymphocytes without in vitro activation. Immunology. ,vol. 76, pp. 338- 340 ,(1992)
Duojia Cao, Ronald van Vollenhoven, Lars Klareskog, Christina Trollmo, Vivianne Malmström, CD25brightCD4+ regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease Arthritis Research & Therapy. ,vol. 6, pp. 42- 42 ,(2004) , 10.1186/AR1192
Ilona Kryczek, Shuang Wei, Linhua Vatan, June Escara-Wilke, Wojciech Szeliga, Evan T. Keller, Weiping Zou, Cutting edge: opposite effects of IL-1 and IL-2 on the regulation of IL-17+ T cell pool IL-1 subverts IL-2-mediated suppression. Journal of Immunology. ,vol. 179, pp. 1423- 1426 ,(2007) , 10.4049/JIMMUNOL.179.3.1423
L REBEKKA RYDER, ELSE MARIE BARTELS, ANDERS WOETMANN, HANS OLE MADSEN, NIELS ØDUM, HENNING BLIDDAL, BENTE DANNESKIOLD-SAMSØE, SØREN RIBEL-MADSEN, LARS P RYDER, FoxP3 mRNA splice forms in synovial CD4+ T cells in rheumatoid arthritis and psoriatic arthritis Apmis. ,vol. 120, pp. 387- 396 ,(2012) , 10.1111/J.1600-0463.2011.02848.X
D. Guschin, N. Rogers, J. Briscoe, B. Witthuhn, D. Watling, F. Horn, S. Pellegrini, K. Yasukawa, P. Heinrich, G.R. Stark, A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. The EMBO Journal. ,vol. 14, pp. 1421- 1429 ,(1995) , 10.1002/J.1460-2075.1995.TB07128.X
Christi Parham, Madaline Chirica, Jacqueline Timans, Elena Vaisberg, Marilyn Travis, Jeanne Cheung, Stefan Pflanz, Rebecca Zhang, Komal P. Singh, Felix Vega, Wayne To, Janet Wagner, Anne-Marie O’Farrell, Terrill McClanahan, Sandra Zurawski, Charles Hannum, Daniel Gorman, Donna M. Rennick, Robert A. Kastelein, Rene de Waal Malefyt, Kevin W. Moore, A Receptor for the Heterodimeric Cytokine IL-23 Is Composed of IL-12Rβ1 and a Novel Cytokine Receptor Subunit, IL-23R Journal of Immunology. ,vol. 168, pp. 5699- 5708 ,(2002) , 10.4049/JIMMUNOL.168.11.5699
Matthew A. Burchill, Jianying Yang, Christine Vogtenhuber, Bruce R. Blazar, Michael A. Farrar, IL-2 Receptor β-Dependent STAT5 Activation Is Required for the Development of Foxp3+ Regulatory T Cells Journal of Immunology. ,vol. 178, pp. 280- 290 ,(2007) , 10.4049/JIMMUNOL.178.1.280
Jin-Sil Park, Jennifer Lee, Mi-Ae Lim, Eun-Kyung Kim, Sung-Min Kim, Jun-Geol Ryu, Jae Ho Lee, Seung-Ki Kwok, Kyung-Su Park, Ho-Youn Kim, Sung-Hwan Park, Mi-La Cho, JAK2-STAT3 Blockade by AG490 Suppresses Autoimmune Arthritis in Mice via Reciprocal Regulation of Regulatory T Cells and Th17 Cells Journal of Immunology. ,vol. 192, pp. 4417- 4424 ,(2014) , 10.4049/JIMMUNOL.1300514
Hideaki Sugiyama, Rolland Gyulai, Eiko Toichi, Edina Garaczi, Shinji Shimada, Seth R. Stevens, Thomas S. McCormick, Kevin D. Cooper, Dysfunctional Blood and Target Tissue CD4+CD25high Regulatory T Cells in Psoriasis: Mechanism Underlying Unrestrained Pathogenic Effector T Cell Proliferation The Journal of Immunology. ,vol. 174, pp. 164- 173 ,(2005) , 10.4049/JIMMUNOL.174.1.164