Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis

Bregje Berge, Marthe Paats, Ingrid Bergen, B Blink, Henk Hoogsteden, Bart Lambrecht, Rudi Hendriks, Alex Kleinjan

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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 IL17A/IFN-gamma 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-17 Conclusions. Enhanced IL-17A expression in granulomas and the presence of IL-17A(+), IL-17A(+) IFN-gamma(+) 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.
Original languageUndefined/Unknown
Pages (from-to)37-46
Number of pages10
JournalRheumatology
Volume51
Issue number1
DOIs
Publication statusPublished - 2012

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