Vitamin D-deficiency induces eosinophil spontaneous activation

Abstract

Eosinophils (Eo) play a critical role in immunity and immune inflammation. The maintenance of Eo homeostasis is not fully understood yet. Vitamin D (VitD) is involved in the regulation of a large number of biochemical reactions. This study tests a hypothesis that VitD receptor (VDR) contributes to the homeostasis of Eos. In this study, EoL-1 cells (an Eo cell line) were cultured in the presence or absence of calcitriol. The Eo-mediators, including major basic protein (MBP), Eo peroxidase (EPX), Eo cationic protein (ECP) and Eo-derived neurotoxin (EDN), were assessed in the culture supernatant and in EoL-1 cells. We observed that, in a VitD deficient environment, EoL-1 cells produced high levels of the Eo-mediators, including MBP, EPX, ECP and EDN, which could be suppressed by the addition of calcitriol to the culture. EoL-1 cells expressed VitD receptor (VDR), which was up regulated by exposure to calcitriol. VDR formed complexes with the transcription factors of the Eo-mediators, which prevented the transcription factors to bind to the promoters of the Eo-mediators, and therefore prevented the Eo-mediated gene transcription. The Eo spontaneous activation was also found in the intestinal mucosa of VDR-deficient mice, in which the intestinal epithelial barrier dysfunction was observed. In conclusion, VDR contributes to the maintenance of the homeostasis of Eos by regulating the gene transcription of the Eo mediators. The VDR-deficiency is one of the causative factors inducing Eo spontaneous activation. This phenomenon may be taken into account in the management of the Eo-related diseases.