RT Journal Article
SR Electronic
T1 Sarcoidosis is a Th1/Th17 multisystem disorder
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 144
OP 150
DO 10.1136/thx.2010.140319
VO 66
IS 2
A1 Monica Facco
A1 Anna Cabrelle
A1 Antonella Teramo
A1 Valeria Olivieri
A1 Marianna Gnoato
A1 Sara Teolato
A1 Elisa Ave
A1 Cristina Gattazzo
A1 Gian Paolo Fadini
A1 Fiorella Calabrese
A1 Gianpietro Semenzato
A1 Carlo Agostini
YR 2011
UL http://thorax.bmj.com/content/66/2/144.abstract
AB 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.