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Original article
Sarcoidosis is a Th1/Th17 multisystem disorder
  1. Monica Facco1,2,
  2. Anna Cabrelle2,
  3. Antonella Teramo1,2,
  4. Valeria Olivieri1,2,
  5. Marianna Gnoato2,
  6. Sara Teolato1,
  7. Elisa Ave1,2,
  8. Cristina Gattazzo1,2,
  9. Gian Paolo Fadini3,
  10. Fiorella Calabrese4,
  11. Gianpietro Semenzato1,2,
  12. Carlo Agostini1,2
  1. 1Department of Clinical and Experimental Medicine, Hematology-Immunology Section, Padua University School of Medicine, Padova, Italy
  2. 2Venetian Institute of Molecular Medicine, Padua University School of Medicine, Padova, Italy
  3. 3Department of Clinical and Experimental Medicine, Metabolic Diseases, Padua University School of Medicine, Padova, Italy
  4. 4Department of Diagnostic Medical Sciences and Special Therapies, Padua University School of Medicine, Padova, Italy
  1. Correspondence to Carlo Agostini, Padua University School of Medicine, Department of Clinical and Experimental Medicine, Hematology and Clinical Immunology Section, Via Giustiniani 2, 35128 Padova, Italy; carlo.agostini{at}unipd.it

Abstract

Background and aims Sarcoidosis is characterised by a compartmentalisation of CD4+ T helper 1 (Th1) lymphocytes and activated macrophages in involved organs, including the lung. Recently, Th17 effector CD4+ T cells have been claimed to be involved in the pathogenesis of granuloma formation. The objective of this study was to investigate the involvement of Th17 cells in the pathogenesis of sarcoidosis.

Methods Peripheral and pulmonary Th17 cells were evaluated by flow cytometry, real-time PCR, immunohistochemistry analyses and functional assays in patients with sarcoidosis in different phases of the disease and in control subjects.

Results Th17 cells were detected both in the peripheral blood (4.72±2.27% of CD4+ T cells) and in the bronchoalveolar lavage (BAL) (8.81±2.25% of CD4+ T lymphocytes) of patients with sarcoidosis and T cell alveolitis. Immunohistochemical analysis of lung and lymph node specimens showed that interleukin 17 (IL-17)+/CD4+ T cells infiltrate sarcoid tissues surrounding the central core of the granuloma. IL-17 was expressed by macrophages infiltrating sarcoid tissue and/or forming the granuloma core (7.88±2.40% of alveolar macrophages). Analysis of some lung specimens highlighted the persistence of IL-17+/CD4+ T cells in relapsed patients and their absence in the recovered cases. Migratory assays demonstrated the ability of the Th17 cell to respond to the chemotactic stimulus CCL20—that is, the CCR6 ligand (74.8±8.5 vs 7.6±2.8 migrating BAL lymphocytes/high-powered field, with and without CCL20, respectively).

Conclusions Th17 cells participate in the alveolitic/granuloma phase and also to the progression towards the fibrotic phase of the disease. The recruitment of this cell subset may be driven by CCL20 chemokine.

  • Th17
  • sarcoidosis
  • macrophages
  • lung
  • CCR6
  • lung physiology
  • lymphocyte biology
  • macrophage biology
  • systemic disease and lungs

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Supplementary materials

  • Web Only Data thx.2010.140319

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Footnotes

  • Funding MF has received a grant from Padua University, Progetto di Ateneo CPDA063349/06. GS (PRIN 2007) and CA (PRIN 2009) have received grants from the Italian Ministry of University, Research, and Education, Rome (Italy).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Padova Hospital Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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