HLA-DR⁺CD38⁺ activated Th17.1 cells reflect disease activity and corticosteroid responsiveness in pulmonary sarcoidosis

Sarcoidosis is a systemic granulomatous disease caused by sustained activation of CD4⁺ T cells following exposure to unknown antigens. Th17.1 cells appear to play important roles in the pathophysiology of pulmonary sarcoidosis by differentiating from Th17 cells through interactions with antigen-presenting cells and producing large amounts of interferon gamma. However, whether these cells promote or inhibit granulomatous inflammation and how regulatory T cells, which suppress the activity of these cells, are involved in the pathogenesis of sarcoidosis remains unclear. This exploratory study aimed to elucidate the roles of Th17.1 cells and regulatory T cells in the pathophysiology of pulmonary sarcoidosis.

We compared and evaluated the proportions and activation states of Th17.1 cells and regulatory T cells in peripheral blood (n = 34) and bronchoalveolar lavage fluid (n = 22) from patients with pulmonary sarcoidosis, and from patients with connective tissue disease-associated interstitial lung disease (n = 36, 34). We also conducted a longitudinal investigation of changes before and after corticosteroid treatment and associations with disease progression.

The proportion of activated Th17.1 cells was higher in peripheral blood and bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis than from patients with connective tissue disease-associated interstitial lung disease. However, this proportion decreased with corticosteroid administration and was associated with disease progression. The proportion of regulatory T cells was significantly lower in the lungs of sarcoidosis patients compared to those with connective tissue disease-associated interstitial lung disease.

Among patients with corticosteroid-responsive pulmonary sarcoidosis, activation of Th17.1 cells reflects disease activity.