title: Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis.
abstract: OBJECTIVE
  IL-9 has been shown to be upregulated before the clinical onset of articular disease in RA. The exact role of IL-9 and Th9 cells in RA, however, has not yet been adequately studied. The aim of this study was to evaluate the expression of IL-9 and IL-9-expressing cells in RA patients.
  
  
  METHODS
  IL-9, IL-9R, PU.1, IL-9, thymic stromal lymphopoietin (TSLP), IL-4 and TGF-β expression was assessed by real-time-PCR in the synovial tissues of RA and OA patients. IL-9, IL-9R, IL-4, TSLP and TGF-β were also investigated by immunohistochemistry. Peripheral CD4(+) T cell subsets were studied by flow cytometry analysis before and after incubation with citrullinated peptides.
  
  
  RESULTS
  IL-9 was overexpressed in RA synovial tissues and correlated with the degree of histological organization of B and T cells in ectopic lymphoid structures. The majority of IL-9-producing cells were identified as CD3(+) cells. Increased mRNA and protein expression of IL-9R, IL-4, TSLP and TGF-β was also observed in RA synovial tissue. Blood peripheral Th9 cells were expanded by citrullinated peptides.
  
  
  CONCLUSIONS
  These results indicate that Th9 cells and IL-9 were frequently detected in peripheral blood mononuclear cells and synovia of RA patients. A possible pathogenic role for Th9 in RA is discussed.
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ciccia
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Guggino
authors.affiliation: Azienda Ospedaliera Ospedali riuniti Villa Sofia-Cervello, Anatomia Patologica, Palermo and.
authors.forename: Aroldo
authors.initials: A
authors.lastname: Rizzo
authors.affiliation: Rheumatology and Translational Immunology Research Laboratories, Division of Rheumatology, IRCCS Policlinico San Matteo/University of Pavia, Pavia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Manzo
authors.affiliation: Rheumatology and Translational Immunology Research Laboratories, Division of Rheumatology, IRCCS Policlinico San Matteo/University of Pavia, Pavia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Vitolo
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo.
authors.forename: Marco Pio
authors.initials: MP
authors.lastname: La Manna
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Giardina
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo.
authors.forename: Guido
authors.initials: G
authors.lastname: Sireci
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
authors.affiliation: Rheumatology and Translational Immunology Research Laboratories, Division of Rheumatology, IRCCS Policlinico San Matteo/University of Pavia, Pavia, Italy.
authors.forename: Carlo Maurizio
authors.initials: CM
authors.lastname: Montecucco
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Alessandro
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, giovanni.triolo@unipa.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Triolo
mesh_terms: D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis; D016906:Interleukin-9 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D013583:Synovial Membrane / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D016906:Interleukin-9; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin
keywords: IL-9; Th9 cells; citrullinated peptide; rheumatoid arthritis