Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis
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. 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. 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. 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.
|Keywords||Bronchoalveolar Lavage Fluid - immunology, Granuloma - immunology, Granuloma - pathology, Interferon-gamma - metabolism, Interleukin-17 - metabolism, Interleukin-17 - physiology, Interleukins - metabolism, Lung - pathology, Sarcoidosis, Pulmonary - immunology, Sarcoidosis, Pulmonary - pathology, T-Lymphocyte Subsets - immunology, Th17 Cells - immunology, Tumor Necrosis Factor-alpha - metabolism|
|Persistent URL||dx.doi.org/10.1093/rheumatology/ker316, hdl.handle.net/1765/37175|
ten Berge, B., Paats, M.S., Bergen, I.M., van den Blink, B., Hoogsteden, H.C., Lambrecht, B.N., … Kleinjan, A.. (2012). Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis. Rheumatology (Oxford, England), 51(1), 37–46. doi:10.1093/rheumatology/ker316