title: JAK/STAT/PKCδ molecular pathways in synovial fluid T lymphocytes reflect the in vivo T helper-17 expansion in psoriatic arthritis.
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.
authors.affiliation: Rheumatology Unit, Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padua, Italy, ugo.fiocco@unipd.it.
authors.forename: Ugo
authors.initials: U
authors.lastname: Fiocco
authors.forename: Benedetta
authors.initials: B
authors.lastname: Accordi
authors.forename: Veronica
authors.initials: V
authors.lastname: Martini
authors.forename: Francesca
authors.initials: F
authors.lastname: Oliviero
authors.forename: Monica
authors.initials: M
authors.lastname: Facco
authors.forename: Anna
authors.initials: A
authors.lastname: Cabrelle
authors.forename: Lucia
authors.initials: L
authors.lastname: Piva
authors.forename: Beatrice
authors.initials: B
authors.lastname: Molena
authors.forename: Francesco
authors.initials: F
authors.lastname: Caso
authors.forename: Luisa
authors.initials: L
authors.lastname: Costa
authors.forename: Anna
authors.initials: A
authors.lastname: Scanu
authors.forename: Elisa
authors.initials: E
authors.lastname: Pagnin
authors.forename: Mariangela
authors.initials: M
authors.lastname: Atteno
authors.forename: Raffaele
authors.initials: R
authors.lastname: Scarpa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Semenzato
authors.forename: Leonardo
authors.initials: L
authors.lastname: Punzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Doria
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dayer
mesh_terms: D000328:Adult; D015535:Arthritis, Psoriatic / Q000201:enzymology / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053612:Janus Kinases / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis; D051745:Protein Kinase C-delta / Q000276:immunology; D050791:STAT Transcription Factors / Q000276:immunology; D018709:Statistics, Nonparametric; D013582:Synovial Fluid / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology*
chemical_list: D050791:STAT Transcription Factors; D053612:Janus Kinases; D051745:Protein Kinase C-delta; D048049:Extracellular Signal-Regulated MAP Kinases