RT Journal Article
SR Electronic
T1 <em>Ex Vivo</em> Signaling Protein Mapping in T Lymphocytes in the Psoriatic Arthritis Joints
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 48
OP 52
DO 10.3899/jrheum.150636
VO 93
A1 Ugo Fiocco
A1 Veronica Martini
A1 Benedetta Accordi
A1 Francesco Caso
A1 Luisa Costa
A1 Francesca Oliviero
A1 Anna Scanu
A1 Mara Felicetti
A1 Paola Frallonardo
A1 Monica Facco
A1 Daniele Boso
A1 Beatrice Molena
A1 Renato Zambello
A1 Roberta Ramonda
A1 Franco Cozzi
A1 Raffaele Scarpa
A1 Giuseppe Basso
A1 Gianpietro Semenzato
A1 Jean-Michel Dayer
A1 Andrea Doria
A1 Leonardo Punzi
YR 2015
UL http://www.jrheum.org/content/93/48.abstract
AB 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.