title: Interleukin (IL)-9/IL-9R axis drives γδ T cells activation in psoriatic arthritis patients.
abstract: Cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-12, interferon (IFN)-γ, IL-23 and, more recently, IL-9, have been implicated in the initiation/maintenance of inflammation in psoriasis and psoriatic arthritis (PsA). In the present study we aimed to characterize the role of γδ T cells in peripheral blood and synovial fluid of PsA patients and to investigate their response to in-vitro stimulation with antigen or cytokines (IL-9 and IL-23). γδ T cells isolated from peripheral blood mononuclear cells and synovial fluid were analysed by flow cytometry to evaluate the phenotype and cytokine production. IL-23R and IL-9R gene expression were also evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Peripheral blood mononuclear cells (PBMC), sorted γδ T cells and γδ cell lines were also stimulated in vitro with isopentenyl pyrophosphate (IPP), recombinant IL-9 or recombinant IL-23. Our results show an expansion of γδ T cells with a predominant effector memory phenotype in peripheral blood and synovium of untreated PsA patients, which reverses significantly after treatment with anti-TNF-α or anti-IL-12/IL-23R monoclonal antibodies (mAbs). Moreover, in PsA patients γδ T cells activation is driven prevalently by IL-9/IL-9R interaction, and not only by IL-23/IL-23R. Together these findings indicate γδ T cells and IL-9 as new players in the pathogenesis of PsA.
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università degli Studi di Palermo.
authors.forename: G
authors.initials: G
authors.lastname: Guggino
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università degli Studi di Palermo.
authors.forename: F
authors.initials: F
authors.lastname: Ciccia
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR).|Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo.
authors.forename: D
authors.initials: D
authors.lastname: Di Liberto
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR).|Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo.
authors.forename: M
authors.initials: M
authors.lastname: Lo Pizzo
authors.affiliation: Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Sezione di Reumatologia, Università di L'Aquila, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ruscitti
authors.affiliation: Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Sezione di Reumatologia, Università di L'Aquila, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Cipriani
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università degli Studi di Palermo.
authors.forename: A
authors.initials: A
authors.lastname: Ferrante
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR).|Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo.
authors.forename: G
authors.initials: G
authors.lastname: Sireci
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR).|Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo.
authors.forename: F
authors.initials: F
authors.lastname: Dieli
authors.affiliation: UMR 563, Hospital Purpan, Department of Oncology, INSERM, Toulouse, France.
authors.forename: J J
authors.initials: JJ
authors.lastname: Fourniè
authors.affiliation: Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Sezione di Reumatologia, Università di L'Aquila, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Giacomelli
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università degli Studi di Palermo.
authors.forename: G
authors.initials: G
authors.lastname: Triolo
mesh_terms: D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D016906:Interleukin-9 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D053651:Receptors, Interleukin-9 / Q000378:metabolism*; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016906:Interleukin-9; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053651:Receptors, Interleukin-9
keywords: IL-9; IL-9R; psoriatic arthritis; γδ-T cells