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Immunologic Research
Published in: Immunologic Research 1/2014

01-01-2014

JAK/STAT/PKCδ molecular pathways in synovial fluid T lymphocytes reflect the in vivo T helper-17 expansion in psoriatic arthritis

Authors: Ugo Fiocco, Benedetta Accordi, Veronica Martini, Francesca Oliviero, Monica Facco, Anna Cabrelle, Lucia Piva, Beatrice Molena, Francesco Caso, Luisa Costa, Anna Scanu, Elisa Pagnin, Mariangela Atteno, Raffaele Scarpa, Giuseppe Basso, Gianpietro Semenzato, Leonardo Punzi, Andrea Doria, Jean-Michel Dayer

Published in: Immunologic Research | Issue 1/2014

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Abstract

Looking to the sustained psoriatic arthritis (PsA) joint as a model of local human inflammation, this study was designed to assess the T lymphocyte signal transduction pathways potentially involved in this chronic immune-mediated inflammatory process, as characterized by direct ex vivo analysis of T helper (Th)-17 T effector (Teff) cell phenotypes in synovial fluid (SF) and peripheral blood (PB) of clinically active PsA patients. The reverse-phase protein arrays (RPPA) technique was employed to identify STAT3, STAT1, JAK1, JAK2, PKCδ and ERK1/2 phosphoprotein levels on total T cell lysates in SF samples of PsA patients. Frequencies of T CD4+IL-17A-F+ and T CD4+IL-23R+ Th17 cells were quantified in SF and matched PB of PsA patients by flow cytometry and compared with PB of healthy controls (HC). Increased levels of JAK1, STAT3, STAT1 and PKCδ phosphoproteins were found in SF T cells of PsA patients, compared with PB of HC. The expansion of T CD4+IL-17A-F+ cells, as well as of T CD4+ cells expressing IL-23Rp19 (T CD4+ IL-23R+), considered as the pathogenic phenotype of effector Th17 cells, was found to be confined to the joints of PsA patients, as the frequencies of both populations were significantly higher in SF than in matched PB, or in PB of HC. In conclusion, T lymphocyte signal transduction pathway mapping revealed an enhanced activation of JAK1/STAT3/STAT1 and PKCδ phosphoproteins that may drive the local inflammatory process, characterized by the in vivo expansion of T CD4+IL-17A-F+ and T CD4+IL-23R+ Th17 Teff cells in SF of clinically active joints of PsA patients.
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Metadata
Title
JAK/STAT/PKCδ molecular pathways in synovial fluid T lymphocytes reflect the in vivo T helper-17 expansion in psoriatic arthritis
Authors
Ugo Fiocco
Benedetta Accordi
Veronica Martini
Francesca Oliviero
Monica Facco
Anna Cabrelle
Lucia Piva
Beatrice Molena
Francesco Caso
Luisa Costa
Anna Scanu
Elisa Pagnin
Mariangela Atteno
Raffaele Scarpa
Giuseppe Basso
Gianpietro Semenzato
Leonardo Punzi
Andrea Doria
Jean-Michel Dayer
Publication date
01-01-2014
Publisher
Springer US
Published in
Immunologic Research / Issue 1/2014
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-013-8481-0

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