Related Experiment Video
Updated: Aug 15, 2026
Three-Dimensional Cell Culture Models to Investigate the Epithelial Barrier in Eosinophilic Esophagitis
Published on: May 10, 2024
Suppression of eosinophilic airway inflammation by treatment with alpha-galactosylceramide
Yuko Morishima1, Yukio Ishii, Toru Kimura
1Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. mk01a231@md.tsukuba.ac.jp
Abstract:
To clarify the essential role of NKT cells in allergy, we investigated the contribution of NKT cells to the pathogenesis of eosinophilic airway inflammation using alpha-galactosylceramide (alpha-GalCer), a selective ligand for NKT cells. Although continuous administration of alpha-GalCer during ovalbumin (OVA) sensitization increased OVA-specific IgE levels and worsened eosinophil inflammation, a single administration of alpha-GalCer at the time of OVA challenge completely prevented eosinophilic infiltration in wild-type mice. This inhibitory effect of alpha-GalCer was associated with a decrease in airway hyperresponsiveness, an increase in IFN-gamma, and decreases in IL-4, IL-5 and IL-13 levels in the bronchoalveolar lavage fluids. Analysis of lung lymphocytes revealed that production of IFN-gamma increased in NK cells, but not in T or NKT cells, following alpha-GalCer administration. Induction of vascular cell adhesion molecule-1 in the lungs of wild-type mice was also significantly attenuated by treatment with alpha-GalCer. These effects of alpha-GalCer were abrogated in J alpha281-/- mice, which lack NKT cells, and in wild-type mice treated with anti-IFN-gamma Ab. Hence, our data indicate that alpha-GalCer suppresses allergen-induced eosinophilic airway inflammation, possibly by inducing a Th1 bias that results in inhibition of eosinophil adhesion to the lung vessels.
Insights
Alpha-galactosylceramide (alpha-GalCer) can prevent eosinophilic airway inflammation in mice. This suggests a potential therapeutic strategy for allergies by modulating immune responses.
Area of Science:
- Immunology
- Allergy Research
Background:
- NKT cells play a crucial role in allergic responses.
- Eosinophilic airway inflammation is a hallmark of allergic asthma.
Purpose of the Study:
- To investigate the role of NKT cells in allergic airway inflammation using alpha-galactosylceramide (alpha-GalCer).
- To determine the therapeutic potential of alpha-GalCer in a mouse model of allergic asthma.
Main Methods:
- Ovalbumin (OVA)-induced allergic asthma model in wild-type and J alpha281-/- mice.
- Administration of alpha-GalCer at different time points.
- Measurement of OVA-specific IgE, airway hyperresponsiveness, and inflammatory cytokines (IFN-gamma, IL-4, IL-5, IL-13).
- Analysis of lung lymphocytes and vascular cell adhesion molecule-1 (VCAM-1) expression.
Main Results:
- A single administration of alpha-GalCer at the time of OVA challenge prevented eosinophilic infiltration and airway hyperresponsiveness.
- alpha-GalCer treatment led to increased IFN-gamma and decreased IL-4, IL-5, and IL-13 levels.
- IFN-gamma production was enhanced in NK cells, not NKT cells, post-alpha-GalCer.
- alpha-GalCer attenuated VCAM-1 induction in the lungs.
- These effects were dependent on NKT cells and IFN-gamma.
Conclusions:
- Alpha-galactosylceramide (alpha-GalCer) suppresses allergen-induced eosinophilic airway inflammation.
- The mechanism involves inducing a Th1 immune bias, inhibiting eosinophil adhesion via VCAM-1.
- Alpha-GalCer demonstrates potential as a therapeutic agent for allergic airway diseases.
