title: Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis.
abstract: OBJECTIVE
  Sarcoidosis is a systemic inflammatory disorder characterized by granulomas. Although the aetiology is unknown, sarcoidosis is thought to be mediated by Th1 lymphocytes. Recently, IL-17A has been implicated in granuloma formation in various diseases, including tuberculosis. Therefore, we hypothesized that Th17 cells play a role in sarcoidosis, paralleling recent findings in autoimmune diseases such as RA. The aim of our study was to investigate the role of Th17 cells in sarcoidosis.
  
  
  METHODS
  T cells were investigated by intracellular flow cytometry and immunohistochemistry, in blood, bronchoalveolar lavages (BALs) and bronchial mucosal biopsies from a cohort of newly diagnosed sarcoidosis patients and healthy controls.
  
  
  RESULTS
  Circulating memory CD4(+) T-cell populations of sarcoidosis patients contained significantly increased proportions of IL-17A(+) cells when compared with healthy controls. Interestingly, proportions of IL-17A/IFN-γ and IL-17A/IL-4 double-producing cells were significantly increased in blood of sarcoidosis patients and were present in substantial numbers in BAL. In granuloma-containing, but not in non-granulomatous sarcoidosis biopsies, we found significantly increased numbers of IL-17A(+) T cells, located in and around granulomas throughout the lamina propria. IL-22(+) T cells were increased in the subepithelial layer.
  
  
  CONCLUSIONS
  Enhanced IL-17A expression in granulomas and the presence of IL-17A(+), IL-17A(+)IFN-γ(+) and IL-17A(+)IL-4(+)memory Th cells in the circulation and BAL indicate Th17 cell involvement in granuloma induction or maintenance in sarcoidosis. Therefore, neutralization of IL-17A activity may be a novel strategy to treat sarcoidosis.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Bregje
authors.initials: B
authors.lastname: Ten Berge
authors.forename: Marthe S
authors.initials: MS
authors.lastname: Paats
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Bergen
authors.forename: Bernt
authors.initials: B
authors.lastname: van den Blink
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
authors.forename: Alex
authors.initials: A
authors.lastname: Kleinjan
mesh_terms: D000328:Adult; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism* / Q000502:physiology; D007378:Interleukins / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D017565:Sarcoidosis, Pulmonary / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D007371:Interferon-gamma; D020381:Interleukin-17; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22