Extensively disturbance of regulatory T cells - Th17 cells balance in stage II pulmonary sarcoidosis

Abstract

Background: Sarcoidosis is a systemic inflammatory disorder characterized by granulomas. Not enough evidences correlate the derangement of CD4+ T subsets, which have an impact on the therapeutic effects of corticosteroids, with the radiographical staging of sarcoidosis. Here we show the disturbance of CD4+ T subsets in newly diagnosed stage II pulmonary sarcoidosis, which is the most common stage in which corticosteroids treatment is used. Materials and methods: 39 newly diagnosed and treatment-naïve patients and 9 subjects after corticosteroids treatment were included. CD4+ CD45RA+/ CD45RO+ cells, CCR4+ CCR6+ cells, and T regulatory cells (Tregs) were tested by Flow Cytometry Analysis. Th1/Th2, Tregs/Th17 related cytokines and mRNAs, SAA and CCL20 were also measured. The activation of PI3K/PTEN/Akt signaling pathway was detected. Results: Percentages of CD4+CD45RO+ memory T cells and Tregs, serum levels of IL-17A, TGF-β1, IL-6, IFN-γ, IL-10, SAA and CCL20, copies of T-bet, FoxP3, IL-17 and RORc in the periphery were elevated in newly diagnosed stage II pulmonary sarcoidosis patients. Additionally, PI3K/Akt signaling pathway was activated in bronchoalveolar lavage fluid cells. Conclusions: Disturbance of T memory cells, Th1/Th2, and Tregs/Th17 cells, and activation of PI3K/Akt signaling were seen in newly diagnosed stage II pulmonary sarcoidosis, which can be partly ameliorated by corticosteroids treatment.