Th 9 cells in Behçet disease: Possible involvement of IL-9 in pulmonary manifestations.

Behçet disease (BD) is a multisystemic disease some of whose manifestations are characterized by pulmonary involvements. The purpose of the study was to evaluate the level of T-helper type 9 (Th9) cells and the cytokine interleukin (IL)-9 in peripheral blood and in bronchoalveolar lavage (BAL) of patients with Behçet's disease (BD) affected by pulmonary manifestations. Nevertheless, until recently there have been no studies on its role in BD. The Th9 (CD4IL-9T) cell, transcription factor PU.1 and IL-9 mRNA levels, as well as serum and BAL IL-9 concentration, were measured in BD patients and healthy controls. The Th9 cell percentage and absolute number, PU.1 and IL-9 expression levels of BD patients were all increased significantly compared with the control group. Absolute number of Th9 cells was particularly increased in patients with active BD compared to inactive BD patients. The levels of IL-9 associated to Th9 expression depended on BD severity. These parameters were markedly expressed in the BAL of BD patients with pulmonary manifestations. IL-17 and the epithelial inflammatory cytokine TSLP were significantly correlated to IL-9 levels. This cytokine trio decreased in inactive BD patients after corticosteroïd treatment. In addition, IL-9 levels were correlated to CD4 IL-9 cells in BAL and in PBMCs. LPS stimulated PBMCs and macrophages induced increased secretion of IL-9 and the encoding transcription factors PU.1 and IRF4. In conclusion, the expansion of the Th9 cell subset, up-regulation of the PU.1 transcription factor and increased secretion of the IL-9 cytokine may contribute to the pathogenesis of BD, which may be supported by the increased release of IL-17 and TSLP. We provide evidence that Th9 T cells are increased in BD patients with pulmonary manifestations. This suggests an important role of IL-9 in the pathogenesis of BD particularly in patients suffering from lung involvement.