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.

Sarcoidosis

“…20 In contrast, there seems to be an imbalance between Th17 and regulatory T cells (T reg ) cells, as has been described in several inflammatory and autoimmune diseases. 22 T reg cells are decreased in patients with sarcoidosis and do not effectively suppress the development of granulomas. 22 It is possible that several agents can serve as antigenic nidi for sarcoidosis granulomas but the development of the disease is influenced by the host's immune system and genetic composition.…”

“…22 T reg cells are decreased in patients with sarcoidosis and do not effectively suppress the development of granulomas. 22 It is possible that several agents can serve as antigenic nidi for sarcoidosis granulomas but the development of the disease is influenced by the host's immune system and genetic composition. Environmental exposures and infectious organisms have long been considered disease promoters (Table 1).…”

Selected Molecular Events in the Pathogenesis of Sarcoidosis—Recent Advances

“…Both cell subsets were shown to be involved in the pathogenesis of sarcoidosis: Treg cells may play a crucial role in abating the inflammatory process, whereas Th17 cells, by promoting a proinflammatory milieu (IL-17, IL-6, TNFa, GM-CSF) may be responsible for sustained inflammatory reaction. Huang et al have shown the increased Th17/Treg ratio in peripheral blood and BAL fluid in active sarcoidosis, which was normalized with treatment [34]. The same results were reported by Tondell et al [35], who revealed that IFN-g + Th17 cells may represent a pathogenic subset of Th17 cells, which are stimulated to IFN-g production by Th1 cells.…”

Small Cell Lung Cancer with Sarcoidosis in Spontaneous Remission: A Case Report

“…It is interesting that ACE, besides serving as a marker for disease activity, may be involved in T lymphocyte regulation. Angiotensin II has been reported to be chemotactic for T lymphocytes 20 , and regulatory T cells suppressing tumor immunity are decreased in the serum and BALF of patients with sarcoidosis 21,22 , while regulatory T cells are known to accumulate in the tumor to suppress tumor immunity 23 . However, further studies of the natural history of sarcoidosis complicated with malignant tumors are required to elucidate the mechanism underlying the association between sarcoidosis and cancer.…”