Imbalance between Th17 and regulatory T-Cells in sarcoidosis

Abstract

Sarcoidosis is a systemic granulomatous disease, which is thought to result from an aberrant immune response. CD4+ T lymphocytes play an important role in the development of granulomas. Previously, the immunopathogenesis of sarcoidosis was focused on Th1/Th2 disturbances. The aim of this study was to evaluate the balance between newer CD4+ T lymphocytes, i.e., Treg and Th17 cells. In our studies, a decrease in Treg cells and an increase in Th17 cells were observed in the peripheral blood and BALF of sarcoidosis patients. A significant increase in the Th17/Treg cell ratio was observed in sarcoidosis patients. After treatment with prednisone, the expression of Foxp3 mRNA was elevated in the peripheral blood, and expression of (ROR)γt mRNA showed a downward trend. These findings suggest that sarcoidosis is associated with an imbalance between Th17 and Treg cells in peripheral blood and BALF. Therefore, targeting the cytokines that affect the Th17/Treg ratio could provide a new promising therapy for pulmonary sarcoidosis.

Figure 1

Representative plots of Th17 and Treg cells in sarcoidosis patients’ and HCs’ peripheral blood by flow cytometry (A, B, C, D). (A) Physical parameter (forward scatter and side scatter) of lymphocytes in the peripheral blood; (B) Representative dot plots showing CD4⁺ T cells producing IL-17A in sarcoidosis patients’ and HCs’ peripheral blood; (C) Physical parameter (side scatter) and CD4 expression of lymphocytes in the peripheral blood; (D) Representative dot plots showing CD4⁺ T cells producing CD25 and Foxp3 in sarcoidosis patients’ and HCs’ peripheral blood.

Figure 2

Representative plots of Th17 and Treg cells in sarcoidosis patients’ BALF by flow cytometry (A, B, C, D). (A) Physical parameter (forward scatter and side scatter) of lymphocytes in BALF; (B) Physical parameter (side scatter) and CD4 expression of lymphocytes in BALF; (C) Representative dot plots showing CD4⁺ T cells producing IL-17A in sarcoidosis patients’ BALF; (D) Representative dot plots showing CD4⁺ T cells producing CD25 and Foxp3 in sarcoidosis patients’ BALF.

Figure 2

Representative plots of Th17 and Treg cells in sarcoidosis patients’ BALF by flow cytometry (A, B, C, D). (A) Physical parameter (forward scatter and side scatter) of lymphocytes in BALF; (B) Physical parameter (side scatter) and CD4 expression of lymphocytes in BALF; (C) Representative dot plots showing CD4⁺ T cells producing IL-17A in sarcoidosis patients’ BALF; (D) Representative dot plots showing CD4⁺ T cells producing CD25 and Foxp3 in sarcoidosis patients’ BALF.

Figure 3

The percentage of Th17 cells (A) in the PBMC of HCs and sarcoidosis patients (Sar-1), and in the BALF of sarcoidosis patients (Sar-BALF) (*p = 0.0139; ^#p = 0.0016). The percentage of Treg cells (B) in the PBMC of HCs and sarcoidosis patients (Sar-1), and in the BALF of sarcoidosis patients (Sar-BALF) (*p = 0.0286; ^#p = 0.0346). Each datum point represents an individual patient sample. Median values for each group are represented by the horizontal line.

Figure 4

The ratio of Th17/Treg cells in healthy controls (HC) and sarcoidosis patients (Sar-1), and in the BALF of sarcoidosis patients (Sar-BALF).