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Increased Galectin-9 Concentration and Number of CD4+Foxp3high+Cells in Bronchoalveolar Lavage Fluid of Patients with Cryptogenic Organizing Pneumonia

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Abstract

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.

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Acknowledgments

The authors thank Ms. Midori Isobe and Ms. Mariko Takaya for their skilful assistance.

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Authors and Affiliations

  1. Department of Respiratory Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan

    Shigeki Katoh, Masaki Ikeda, Hiroki Shimizu, Masaaki Abe, Yoshihiro Ohue, Keiji Mouri, Yoshihiro Kobashi & Mikio Oka

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  1. Shigeki Katoh
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  2. Masaki Ikeda
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  3. Hiroki Shimizu
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  4. Masaaki Abe
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  5. Yoshihiro Ohue
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  6. Keiji Mouri
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  7. Yoshihiro Kobashi
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  8. Mikio Oka
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Correspondence to Shigeki Katoh.

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Katoh, S., Ikeda, M., Shimizu, H. et al. Increased Galectin-9 Concentration and Number of CD4+Foxp3high+Cells in Bronchoalveolar Lavage Fluid of Patients with Cryptogenic Organizing Pneumonia. Lung 193, 683–689 (2015). https://doi.org/10.1007/s00408-015-9775-x

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  • DOI: https://doi.org/10.1007/s00408-015-9775-x

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