Dysregulation of Th17 and regulatory T Cells in chronic pulmonary sarcoidosis: a potential biomarker for disease management

Sarcoidosis is a multisystem inflammatory disease of unknown etiology characterized by the formation of non-caseating granulomas, most commonly in the lung tissue. It presents with two main forms: acute and chronic. Patients with chronic sarcoidosis tend to have a less favorable prognosis with a risk of developing lung fibrosis. Sarcoidosis development involves the activation of T cells, which release various chemokines and cytokines that stimulate the inflammatory process. The aim of our study was to investigate the role of the ratio between Th17 and Treg cells in the chronic course of sarcoidosis. We studied peripheral blood plasma samples from patients with chronic sarcoidosis (CS) (n = 101) and healthy individuals (HC) (n = 40). The diagnosis in CS patients was confirmed by histological methods. We determined the levels of Th17 and Treg (% of total lymphocytes) by flow cytometry. The concentration of cytokines (pg/ml) IL-17A and IL-10 was measured by multiplex analysis using Luminex xMap. Correlations between the Th17/Treg ratio and clinical parameters, including serum angiotensin-converting enzyme (sACE) activity level in the peripheral blood, forced expiratory volume in the first second (FEV1, %), fibrosis manifestations, and extrapulmonary manifestations were analyzed in CS patients. Our analysis revealed elevated levels of Th17 cells (p = 0.028) and decreased Treg levels (p = 0.026) in CS patients compared to healthy controls. This resulted in a significantly increased Th17/Treg ratio (p = 0.003) and IL-17A/IL-10 ratio (p < 0.001) in sarcoidosis patients. Furthermore, the Th17/Treg ratio positively correlated with sACE levels (p = 0.018), fibrosis manifestations (p = 0.019), and extrapulmonary manifestations (p = 0.016), and negatively correlated with FEV1% (p = 0.021). Our results indicate an increase in the Th17/Treg ratio, as well as the ratio of their main cytokines in patients with chronic sarcoidosis, which may emphasize their potential role as a diagnostic and prognostic biomarker of disease severity. At the molecular level, the balance between Treg and Th17 cells is maintained by the transcription factors Foxp3 and RORγt, which regulate the differentiation and function of these cells. Disruption of this balance in patients with chronic sarcoidosis may indicate a possible mechanism for disease progression.