PURPOSE: Galectin-9 (Gal-9) is a β-galactoside-binding protein that exhibits various biological reactions, such as chemoattraction, cell aggregation, and apoptosis. Recent studies demonstrated that Gal-9 has a role as an immunomodulator in excessive immunological reactions by expanded regulatory T cells (Tregs). We examined the role of Gal-9 in the pathogenesis of one of the major idiopathic interstitial pneumonias, cryptogenic organizing pneumonia (COP) as compared with idiopathic pulmonary fibrosis (IPF). METHODS: Gal-9, transforming growth factor-β1, and interleukin (IL)-10 levels in the bronchoalveolar lavage fluid (BALF) of patients with COP and IPF were estimated by enzyme-linked immunosorbent assay. Forkhead box protein 3 (Foxp3) expressing Tregs were evaluated by flow cytometry. The effect of Gal-9 on interactions between human lung fibroblast cells and hyarulonan was assessed in vitro. RESULTS: Gal-9 and IL-10 levels in the BALF were significantly higher in patients with COP than in patients with IPF. The number of CD4+Foxp3high+cells was significantly higher in the BALF of patients with COP than in those with IPF. Gal-9 levels significantly correlated with the absolute number of CD4+CD25+Foxp3+cells or CD4+Foxp3high+cells, but not with the absolute number of CD4+CD25+Foxp3-cells, in the BALF of patients with COP. Gal-9 suppressed the CD44-dependent interaction of human lung fibroblast cells with hyarulonan in a dose-dependent manner. CONCLUSIONS: Our findings suggest that increased Gal-9 levels in the lung have a protective role against lung inflammation and fibrosis in patients with COP through the induction of Tregs in the lung and CD44-dependent inhibitory effects on lung fibroblast cells.
PURPOSE:Galectin-9 (Gal-9) is a β-galactoside-binding protein that exhibits various biological reactions, such as chemoattraction, cell aggregation, and apoptosis. Recent studies demonstrated that Gal-9 has a role as an immunomodulator in excessive immunological reactions by expanded regulatory T cells (Tregs). We examined the role of Gal-9 in the pathogenesis of one of the major idiopathic interstitial pneumonias, cryptogenic organizing pneumonia (COP) as compared with idiopathic pulmonary fibrosis (IPF). METHODS:Gal-9, transforming growth factor-β1, and interleukin (IL)-10 levels in the bronchoalveolar lavage fluid (BALF) of patients with COP and IPF were estimated by enzyme-linked immunosorbent assay. Forkhead box protein 3 (Foxp3) expressing Tregs were evaluated by flow cytometry. The effect of Gal-9 on interactions between human lung fibroblast cells and hyarulonan was assessed in vitro. RESULTS:Gal-9 and IL-10 levels in the BALF were significantly higher in patients with COP than in patients with IPF. The number of CD4+Foxp3high+cells was significantly higher in the BALF of patients with COP than in those with IPF. Gal-9 levels significantly correlated with the absolute number of CD4+CD25+Foxp3+cells or CD4+Foxp3high+cells, but not with the absolute number of CD4+CD25+Foxp3-cells, in the BALF of patients with COP. Gal-9 suppressed the CD44-dependent interaction of human lung fibroblast cells with hyarulonan in a dose-dependent manner. CONCLUSIONS: Our findings suggest that increased Gal-9 levels in the lung have a protective role against lung inflammation and fibrosis in patients with COP through the induction of Tregs in the lung and CD44-dependent inhibitory effects on lung fibroblast cells.
Authors: Franco R D'Alessio; Kenji Tsushima; Neil R Aggarwal; Erin E West; Matthew H Willett; Martin F Britos; Matthew R Pipeling; Roy G Brower; Rubin M Tuder; John F McDyer; Landon S King Journal: J Clin Invest Date: 2009-09-21 Impact factor: 14.808