Abstract
In sarcoidosis, increased Th17 cell fractions have been reported in bronchoalveolar lavage fluid, and elevated numbers of Th17 cells producing IFN-γ have been observed in peripheral blood. The balance between Th1, Th17, and FoxP3+ CD4+ T cell subsets in sarcoidosis remains unclear. Bronchoalveolar lavage fluid cells, from 30 patients with sarcoidosis, 18 patients with other diffuse parenchymal lung diseases, and 15 healthy controls, were investigated with flow cytometry for intracellular expression of FoxP3. In a subset of the patients, expression of the cytokines IL17A and IFN-γ was investigated. The fractions of FoxP3+ CD4+ T cells and Th17 cells were both lower in sarcoidosis compared to controls (P = 0.017 and P = 0.011, resp.). The proportion of Th17 cells positive for IFN-γ was greater in sarcoidosis than controls (median 72.4% versus 31%, P = 0.0005) and increased with radiologic stage (N = 23, rho = 0.45, and P = 0.03). IFN-γ + Th17 cells were highly correlated with Th1 cells (N = 23, rho = 0.64, and P = 0.001), and the ratio of IFN-γ + Th17/FoxP3+ CD4+ T cells was prominently increased in sarcoidosis. IFN-γ + Th17 cells may represent a pathogenic subset of Th17 cells, yet their expression of IFN-γ could be a consequence of a Th1-polarized cytokine milieu. Our results indicate a possible immune cell imbalance in sarcoidosis.
Highlights
Sarcoidosis is a granulomatous disease with a predilection for the lungs and lymphatic tissue and is characterized by increased fractions and number of IFN-γ-producing T helper cells (Th1 cells) in inflamed tissue [1, 2]
Expression of CD27 and CD39 on FoxP3+ CD4+ T cells was higher in other diffuse parenchymal lung disease (DPLD) compared to sarcoidosis (P = 0.01 and P = 0.03, resp.), and in other DPLDs compared to healthy controls (P = 0.001 and P = 0.02, resp.)
Fractions of bronchoalveolar lavage fluid (BALF) FoxP3+ CD4+ T cells and Th17 cells were lower in sarcoidosis compared to healthy controls
Summary
Sarcoidosis is a granulomatous disease with a predilection for the lungs and lymphatic tissue and is characterized by increased fractions and number of IFN-γ-producing T helper cells (Th1 cells) in inflamed tissue [1, 2]. Whereas regulatory T cells, which are characterized by expression of the transcription factor FoxP3, have a pivotal role in maintaining immune homeostasis and preventing autoimmunity [8, 9]; Th17 cells produce the potent proinflammatory cytokine IL-17 and have a crucial role in host immunity towards extracellular bacterial and fungal pathogens [10]. Both Th17 cells and FoxP3+ CD4+ T cells have been implicated in various human diseases with suspected autoimmune etiology, such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and psoriasis [10,11,12]. Th17 cells recruit Th1 cells to the lungs during a mycobacterial infection and are required for proper formation of granulomas [13]
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