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Galectin-9 Inhibits CD44–Hyaluronan Interaction and Suppresses a Murine Model of Allergic Asthma

¹ Department of Cell Regulation, Faculty of Medicine, Kagawa University, Kagawa, Japan; ² Research Division, GalPharma Company Limited, Kagawa, Japan; Departments of ³ Immunology and Immunopathology, and ⁴ Endocrinology, Faculty of Medicine, Kagawa University, Kagawa, Japan; and ⁵ Division of Human Health and Medical Science, Graduate School of Kuroshio Science, Kochi University, Kochi, Japan

Correspondence and requests for reprints should be addressed to Shigeki Katoh, M.D., Ph.D., Department of Cell Regulation, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. E-mail: kshigeki{at}med.kagawa-u.ac.jp

Rationale: Galectin-9 (Gal-9) belongs to the galectin family, which exhibits affinity for -galactosides. Gal-9 has a variety of biological activities; however, its role in allergic inflammation is unknown.

Objectives: We evaluated the effect of a stable form of the human protein on allergic airway inflammation in a mite allergen–induced asthma model.

Methods: Human stable Gal-9 was given by intravenous injection to mice during antigen challenge. The effect of Gal-9 on airway inflammation and airway hyperresponsiveness (AHR) was then evaluated.

Measurements and Main Results: Gal-9 reduced AHR as well as Th2-associated airway inflammation. Furthermore, administration of Gal-9 as well as anti-CD44 monoclonal antibody inhibited the infiltration of peripheral blood Th2 cells into the airway. Interestingly, Gal-9 directly bound the CD44 adhesion molecule and inhibited interactions with hyaluronan (HA). Consistent with the concept that CD44–HA interactions mediate the migration of T cells into the lung, Gal-9 blocked CD44-dependent adhesion of BW5147 mouse T cells to HA.

Conclusions: We conclude that Gal-9 inhibits allergic inflammation of the airway and AHR by modulating CD44-dependent leukocyte recognition of the extracellular matrix.

Key Words: airway hyperresponsiveness • allergy • experimental model • galectin-9 ligand

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Galectin-9 (Gal-9) is a -galactoside–binding protein that is involved in cell aggregation, adhesion, chemoattraction, activation, and apoptosis. Its role in allergic inflammation had not been reported. What This Study Adds to the Field Gal-9 inhibits allergic asthma in mice. The inhibitory effects of Gal-9 on allergen-induced airway inflammation appear to be due to modulation of CD44-dependent leukocyte recognition of the extracellular matrix.

 

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