CaV1.2 Is Implicated in IgE-Mediated Mast Cell Activation and Food Allergy.

BACKGROUND

Food allergy (FA) is a disorder marked by a significant incidence of detrimental immunological responses to certain dietary constituents, while preventive measures and regulatory treatments are scarce. Mast cells (MCs) are integral to the pathogenesis of FA mediated by Immunoglobulin E (IgE). The activation of MCs is modulated by their intracellular Ca2+ concentrations, with CaV1.2 serving as a voltage-gated calcium channel that regulates calcium influx in MCs.

OBJECTIVE

The aim of this study was to examine the influence of CaV1.2 on MCs' activation and its role in the onset and progression of FA.

METHODS

The inhibitory effect of nimodipine (Nim) on MCs activation in vitro was evaluated by detecting LAD2 degranulation and cytokine release; the anti-food allergy effect of Nim was examined by the establishment of an IgE-mediated FA model; the effect of CaV1.2 on the occurrence of FA was investigated using conditional knockout of CaV1.2 in MCs (CKO) mice.

RESULTS

Nim inhibited MCs activation in vitro and alleviated ovalbumin (OVA)-induced FA in vivo. The expression of CaV1.2 in MCs exhibited detrimental effects, whereas its deficiency ameliorated local and systemic allergy and significantly alleviated FA in mice. When CaV1.2 was replenished in CKO mice by BMMC injection, such supplementation exacerbated FA symptoms.

CONCLUSION

Depression of CaV1.2 in MCs attenuates the activation of MCs and alleviates the symptoms of FA. These results suggest that CaV1.2 could be a new target for FA.