TY - JOUR T1 - <em>Ex Vivo</em> Signaling Protein Mapping in T Lymphocytes in the Psoriatic Arthritis Joints JF - The Journal of Rheumatology JO - J Rheumatol SP - 48 LP - 52 DO - 10.3899/jrheum.150636 VL - 93 AU - Ugo Fiocco AU - Veronica Martini AU - Benedetta Accordi AU - Francesco Caso AU - Luisa Costa AU - Francesca Oliviero AU - Anna Scanu AU - Mara Felicetti AU - Paola Frallonardo AU - Monica Facco AU - Daniele Boso AU - Beatrice Molena AU - Renato Zambello AU - Roberta Ramonda AU - Franco Cozzi AU - Raffaele Scarpa AU - Giuseppe Basso AU - Gianpietro Semenzato AU - Jean-Michel Dayer AU - Andrea Doria AU - Leonardo Punzi Y1 - 2015/11/01 UR - http://www.jrheum.org/content/93/48.abstract N2 - We assessed signaling protein mapping in total T cells, to analyze the proportions of T regulatory (Treg) and TCD4+ effector (Teff) cell phenotypes, and the respective interleukin 6Rα (IL-6Rα) expression in the inflammatory microenvironment of synovial fluid (SF) of patients with sustained psoriatic arthritis (PsA). Our approach was to measure the IL-6 level in SF using a multiplex bead immunoassay. Reverse-phase protein array was used to assess Janus kinase (JAK) 1 and JAK2, extra-cellular regulated kinase (ERK) 1 and 2, protein kinase Cδ (PKCδ), signal transducer and activator and transcription (STAT) 1, STAT3, and STAT5 phosphoproteins in total T cell lysates from SF of patients with PsA. Frequencies of CD4+IL-17A-F+IL-23+ CD4+ Th cells producing IL-17A and IL-17F (Th17) and CD4+CD25high intracellular forkhead box transcription factor+ (FOXP3+) phenotypes, and the percentage of Treg– and Teff– cells were quantified in SF and matched peripheral blood (PB) of patients with PsA and PB of healthy controls (HC) by flow cytometry. Our results were the following: In PsA SF samples, a coordinate increase of JAK1, ERK1/2, STAT1, STAT3, and STAT5 phosphoproteins was found in total T cells in SF of PsA; where IL-6 levels were higher than in PB from HC. Expanded CD4+IL-17A–F+IL-23+ Th17, CD4+ CD25– Teff– and CD4+CD25high FoxP3+Treg subsets, showing similar levels of enhanced IL-6Rδ expression, were confined to PsA joints. In our studies, the transcriptional network profile identified by ex vivo signaling protein mapping in T lymphocytes in PsA joints revealed the complex interplay between IL-1, IL-6, and IL-23 signaling and differentiation of Th17 cells and CD4+Tregs in sustained joint inflammation in PsA. ER -