Galectin-9 is a high affinity IgE-binding lectin with anti-allergic effect by blocking IgE-antigen complex formation

Area of Science:

• Immunology
• Allergology

Background:

• Galectin-9 (Gal-9) is a known immunomodulator with incompletely understood functions.
• Research is exploring Gal-9's role in various disease models to uncover novel activities.

Purpose of the Study:

• To investigate the effects of Galectin-9 (Gal-9) in animal models of allergic diseases.
• To elucidate the mechanism by which Gal-9 modulates mast cell activity.

Main Methods:

• Gal-9's effect on asthmatic reactions in guinea pigs and passive-cutaneous anaphylaxis in mice was assessed.
• In vitro studies utilized RBL-2H3 cells to examine Gal-9's impact on mast cell degranulation.
• Lectin activity was tested using lactose, and Gal-9's binding to immunoglobulin E (IgE) was analyzed.

Main Results:

• Gal-9 significantly attenuated asthmatic reactions and suppressed passive-cutaneous anaphylaxis.
• Gal-9 inhibited IgE plus antigen-induced mast cell degranulation in vitro, an effect dependent on its lectin activity.
• Gal-9 specifically bound to IgE, preventing IgE-antigen complex formation and thereby inhibiting degranulation.
• Gal-9 secretion from mast cells was augmented by immunological stimuli, suggesting an autocrine regulatory role.

Conclusions:

• Galectin-9 exhibits mast cell-stabilizing properties, crucial for its anti-allergic effects.
• The lectin activity of Gal-9 is essential for its interaction with IgE and subsequent suppression of mast cell degranulation.
• Gal-9 acts as an autocrine regulator of mast cell function, potentially offering a therapeutic strategy for allergic disorders such as asthma.