Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis

Francesco Ciccia, Giuliana Guggino, Aroldo Rizzo, Antonio Manzo, Barbara Vitolo, Marco Pio La Manna, Giuseppina Giardina, Guido Sireci, Francesco Dieli, Carlo Maurizio Montecucco, Riccardo Alessandro, Giovanni Triolo

Research output: Contribution to journalArticle

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. Conclusion. 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.

Original languageEnglish
Pages (from-to)2264-2272
Number of pages9
JournalRheumatology
Volume54
Issue number12
DOIs
Publication statusPublished - 2015

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Interleukin-9
Rheumatoid Arthritis
Interleukin-4
Peptides
Synovial Fluid
T-Lymphocyte Subsets
Real-Time Polymerase Chain Reaction
Blood Cells
Flow Cytometry
B-Lymphocytes
Joints
Immunohistochemistry

Keywords

  • Citrullinated peptide
  • IL-9
  • Rheumatoid arthritis
  • Th9 cells

ASJC Scopus subject areas

  • Rheumatology
  • Medicine(all)
  • Pharmacology (medical)

Cite this

Ciccia, F., Guggino, G., Rizzo, A., Manzo, A., Vitolo, B., Manna, M. P. L., ... Triolo, G. (2015). Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis. Rheumatology, 54(12), 2264-2272. https://doi.org/10.1093/rheumatology/kev252

Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis. / Ciccia, Francesco; Guggino, Giuliana; Rizzo, Aroldo; Manzo, Antonio; Vitolo, Barbara; Manna, Marco Pio La; Giardina, Giuseppina; Sireci, Guido; Dieli, Francesco; Montecucco, Carlo Maurizio; Alessandro, Riccardo; Triolo, Giovanni.

In: Rheumatology, Vol. 54, No. 12, 2015, p. 2264-2272.

Research output: Contribution to journalArticle

Ciccia, F, Guggino, G, Rizzo, A, Manzo, A, Vitolo, B, Manna, MPL, Giardina, G, Sireci, G, Dieli, F, Montecucco, CM, Alessandro, R & Triolo, G 2015, 'Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis', Rheumatology, vol. 54, no. 12, pp. 2264-2272. https://doi.org/10.1093/rheumatology/kev252
Ciccia, Francesco ; Guggino, Giuliana ; Rizzo, Aroldo ; Manzo, Antonio ; Vitolo, Barbara ; Manna, Marco Pio La ; Giardina, Giuseppina ; Sireci, Guido ; Dieli, Francesco ; Montecucco, Carlo Maurizio ; Alessandro, Riccardo ; Triolo, Giovanni. / Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis. In: Rheumatology. 2015 ; Vol. 54, No. 12. pp. 2264-2272.
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AU - Guggino, Giuliana

AU - Rizzo, Aroldo

AU - Manzo, Antonio

AU - Vitolo, Barbara

AU - Manna, Marco Pio La

AU - Giardina, Giuseppina

AU - Sireci, Guido

AU - Dieli, Francesco

AU - Montecucco, Carlo Maurizio

AU - Alessandro, Riccardo

AU - Triolo, Giovanni

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N2 - 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. Conclusion. 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.

AB - 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. Conclusion. 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.

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