Inhibition effect of blunting Notch signaling on food allergy through improving T1/T2 balance in mice.

BACKGROUND

Notch signaling regulates proliferation, differentiation, and function of dendritic cells, T cells, and mast cells, as well as many other immune cells, which act as important parts in food allergy, Notch signaling may play an important role in food allergy.

OBJECTIVE

To investigate the role of Notch signaling in IgE-mediated food allergy.

METHODS

An ovalbumin-induced food allergy mouse model was built (cholera toxin as adjuvant) and Notch signaling was blunted by FLI-06 and MW167, which inhibited Notch receptor-expressing phase and the γ-secretase-affecting phase, respectively. Then food allergy indicators, including levels of serum antibodies, cytokines, and degranulation, were examined. Meanwhile, clinical features, such as vascular permeability changes, intestinal permeability changes, body temperature changes, and symptoms, were also observed.

RESULTS

After blunting Notch signaling, the levels of serum ovalbumin specific IgE and IgG were decreased significantly, suggesting that blunting Notch signaling inhibited antibody responses. The levels of T1 cytokines (interferon-γ) were increased significantly, whereas the levels of T2 cytokines (interleukin-4, -5, and -13) were decreased significantly, suggesting T2 polarization was suppressed after blunting Notch signaling. The expression of T-bet was significantly increased, whereas the expression of Gata-3 was significantly reduced in both messenger RNA and protein levels, indicating T2 polarization was inhibited and T1 polarization was enhanced after blunting Notch signaling. Moreover, allergic clinical features of mice were alleviated after blunting Notch signaling.

CONCLUSION

Food allergy was inhibited by blunting Notch signaling through suppressing T2 polarization, enhancing T1 cell differentiation and promoting T1/T2 balance in mice. Notch signaling plays a key role in IgE-mediated food allergy.