Sarcoidosis is a Th1/Th17 multisystem disorder.
OBJECTIVE
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.
Padua University School of Medicine, Department of Clinical and Experimental Medicine, Hematology and Clinical Immunology Section, Via Giustiniani 2, 35128 Padova, Italy.
Monica
M
Facco
Anna
A
Cabrelle
Antonella
A
Teramo
Valeria
V
Olivieri
Marianna
M
Gnoato
Sara
S
Teolato
Elisa
E
Ave
Cristina
C
Gattazzo
Gian Paolo
GP
Fadini
Fiorella
F
Calabrese
Gianpietro
G
Semenzato
Carlo
C
Agostini
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D008168:Lung / Q000276:immunology; D008297:Male; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D017565:Sarcoidosis, Pulmonary / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
C515500:IL23R protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D018123:Receptors, Interleukin