Ca
V
1.2
Is Implicated in IgE‐Mediated Mast Cell Activation and Food Allergy
Tingting Deng, Wen Zhang, Jiahui Meng, Jie Gao, Chang Gao, Shiyu Li, Jiaxing Wang, Zijian Zeng, Yongjing Zhang, Nan Wang ABSTRACT
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 Ca 2+ concentrations, with Ca V 1.2 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 Ca V 1.2 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 Ca V 1.2 on the occurrence of FA was investigated using conditional knockout of Ca V 1.2 in MCs (CKO) mice.
Results
Nim inhibited MCs activation in vitro and alleviated ovalbumin (OVA)‐induced FA in vivo. The expression of Ca V 1.2 in MCs exhibited detrimental effects, whereas its deficiency ameliorated local and systemic allergy and significantly alleviated FA in mice. When Ca V 1.2 was replenished in CKO mice by BMMC injection, such supplementation exacerbated FA symptoms.
Conclusion
Depression of Ca V 1.2 in MCs attenuates the activation of MCs and alleviates the symptoms of FA. These results suggest that Ca V 1.2 could be a new target for FA.