title: Interleukin-9 Overexpression and Th9 Polarization Characterize the Inflamed Gut, the Synovial Tissue, and the Peripheral Blood of Patients With Psoriatic Arthritis.
abstract: To investigate the expression and tissue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA).
  
  
  
  Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA-B27-positive patients with ankylosing spondylitis (AS), patients with Crohn's disease (CD), and healthy controls. Expression and tissue distribution of interleukin-23 (IL-23), IL-17, IL-22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohistochemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among peripheral blood, lamina propria, and synovial fluid mononuclear cells. The functional relevance of IL-9R expression on epithelial cells was assessed in functional in vitro studies. Th9 cells in synovial tissue from patients with PsA were also studied.
  
  
  
  Subclinical gut inflammation in PsA patients was characterized by a clear Th17 and Th22, but not Th1, polarized immune response. Unlike AS and CD, a strong and significant up-regulation of IL-9 was observed in PsA gut, especially among infiltrating mononuclear cells, high endothelial venules, and Paneth cells. IL-9-positive mononuclear cells were demonstrated to be in large part Th9 cells. IL-9 overexpression was accompanied by significant Paneth cell hyperplasia. Paneth cells strongly overexpressed IL-9R, and stimulation of epithelial cells, isolated from PsA patients, with IL-9 resulted in overexpression of α-defensin 5 and IL-23p19. Peripheral and synovial expansion of α4β7+ Th9 cells was also observed in patients with PsA. Increased expression of IL-9 and IL-9R was also found in synovial tissue.
  
  
  
  Strong IL-9/Th9 polarization seems to be the predominant immunologic signature in patients in PsA.
authors.affiliation: Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ciccia
authors.affiliation: Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Guggino
authors.affiliation: Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Ferrante
authors.affiliation: Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Raimondo
authors.affiliation: Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Bignone
authors.affiliation: Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Rodolico
authors.affiliation: Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Peralta
authors.affiliation: Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Melissa
authors.initials: M
authors.lastname: Van Tok
authors.affiliation: Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cannizzaro
authors.affiliation: Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schinocca
authors.affiliation: Università di L'Aquila, Palermo, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruscitti
authors.affiliation: Università di L'Aquila, Palermo, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cipriani
authors.affiliation: Università di L'Aquila, Palermo, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giacomelli
authors.affiliation: Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Alessandro
authors.affiliation: Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
authors.affiliation: Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
authors.forename: Aroldo
authors.initials: A
authors.lastname: Rizzo
authors.affiliation: Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
authors.affiliation: Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Triolo
mesh_terms: D015535:Arthritis, Psoriatic / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D016906:Interleukin-9 / Q000096:biosynthesis* / Q000235:genetics; D007422:Intestines; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors; D013583:Synovial Membrane; D006377:T-Lymphocytes, Helper-Inducer; D000069549:Ustekinumab / Q000627:therapeutic use
chemical_list: D016906:Interleukin-9; D018124:Receptors, Tumor Necrosis Factor; D000069549:Ustekinumab