title: Transcriptional network profile on synovial fluid T cells in psoriatic arthritis.
abstract: The objective of the study was to quantify the transcriptional profile, as the main T cell lineage-transcription factors on synovial fluid (SF) T cells, in relation to SF cytokines and T cell frequencies (%) of psoriatic arthritis (PsA) patients. Reverse phase protein array was employed to identify interleukin (IL)-23Rp19-, FOXP3- and related orphan receptor gamma T (RORγt)- protein and Janus associated tyrosine kinases 1 (JAK1), signal transducer and activator and transcription 1 (STAT1), STAT3 and STAT5 phosphoproteins in total T cell lysates from SF of PsA patients. IL-1β, IL-2, IL-6, IL-21 and interferon (INF)-γ were measured using a multiplex bead immunoassay in SF from PsA patients and peripheral blood (PB) from healthy controls (HC). Frequencies of CD4(+)CD25(-), CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg, and either mean fluorescence intensity (MFI) of FOXP3(+) on CD4(+) Treg or MFI of classic IL-6 receptor (IL-6R) α expression on CD4(+)CD25(-) helper/effector T cells (Th/eff) and Treg cells, were quantified in SF of PsA patients and in PB from HC by flow cytometry (FC). In PsA SF samples, IL-2, IL-21 and IFN-γ were not detectable, whereas IL-6 and IL-1β levels were higher than in SF of non-inflammatory osteoarthritis patients. Higher levels of IL-23R-, FOXP3- and RORγt proteins and JAK1, STAT1, STAT3 and STAT5 were found in total T cells from SF of PsA patients compared with PB from HC. Direct correlations between JAK1 Y1022/Y1023 and STAT5 Y694, and STAT3 Y705 and IL6, were found in SF of PsA patients. Increased proportion of CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg cells and brighter MFI of IL-6Rα were observed both on CD4(+)CD25(high)- and CD4(+)CD25(-) T cells in PsA SF. The study showed a distinctive JAK1/STAT3/STAT5 transcriptional network on T cells in the joint microenvironment, outlining the interplay of IL-6, IL-23, IL-1β and γC cytokines in the polarization and plasticity of Th17 and Treg cells, which might participate in the perpetuation of joint inflammation in PsA patients.
authors.affiliation: Rheumatology Unit, Department of Medicine DIMED, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy, ugo.fiocco@unipd.it.
authors.forename: Ugo
authors.initials: U
authors.lastname: Fiocco
authors.forename: Veronica
authors.initials: V
authors.lastname: Martini
authors.forename: Benedetta
authors.initials: B
authors.lastname: Accordi
authors.forename: Francesco
authors.initials: F
authors.lastname: Caso
authors.forename: Luisa
authors.initials: L
authors.lastname: Costa
authors.forename: Francesca
authors.initials: F
authors.lastname: Oliviero
authors.forename: Anna
authors.initials: A
authors.lastname: Scanu
authors.forename: Monica
authors.initials: M
authors.lastname: Facco
authors.forename: Daniele
authors.initials: D
authors.lastname: Boso
authors.forename: Mariele
authors.initials: M
authors.lastname: Gatto
authors.forename: Mara
authors.initials: M
authors.lastname: Felicetti
authors.forename: Paola
authors.initials: P
authors.lastname: Frallonardo
authors.forename: Roberta
authors.initials: R
authors.lastname: Ramonda
authors.forename: Lucia
authors.initials: L
authors.lastname: Piva
authors.forename: Renato
authors.initials: R
authors.lastname: Zambello
authors.forename: Carlo
authors.initials: C
authors.lastname: Agostini
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: Jean-Michel
authors.initials: JM
authors.lastname: Dayer
authors.forename: Leonardo
authors.initials: L
authors.lastname: Punzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Doria
mesh_terms: D000328:Adult; D015535:Arthritis, Psoriatic / Q000276:immunology*; D016207:Cytokines / Q000032:analysis* / Q000145:classification*; D005260:Female; D005434:Flow Cytometry; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D053759:Interleukin-23 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000276:immunology*
chemical_list: D016207:Cytokines; D053759:Interleukin-23; D015850:Interleukin-6