ENT Institute of the Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Longgang ENT Hospital and Shenzhen ENT Institute, Shenzhen, China.
Clin Exp Allergy. 2017 May;47(5):656-664. doi: 10.1111/cea.12894. Epub 2017 Feb 28.
Dendritic cell (DC)-derived immunoglobulin domain molecule (TIM)4 plays a critical role in the initiation of T helper (Th)2 polarization. Vitamin D (VitD) involves the regulation of a number of immune responses.
This study tests a hypothesis that VitD regulates TIM4 expression in DCs.
Peripheral blood samples were collected from patients with allergic rhinitis (AR) and healthy subjects. DCs were isolated from the samples and analyzed for the expression of TIM4.
We observed that the levels of calcitriol, the active form of VitD3, in the sera of AR patients were lower than that in healthy subjects. The peripheral DC expressed higher levels of TIM4 and lower levels of VDR. A negative correlation was identified between the data of serum calcitriol and TIM4 in DCs. Exposure DCs to calcitriol in the culture increased the expression of VDR. We also found that VDR bound to the TIM4 promoter locus in DCs to repress the TIM4 gene transcription and expression.
VitD deficiency may contribute to the pathogenesis of AR by increasing the TIM4 expression. The results suggest that to regulate the serum calcitriol levels and the expression of VDR in DCs may be necessary to be taken into account in the treatment of AR.
树突状细胞(DC)衍生的免疫球蛋白结构域分子(TIM)4 在启动辅助性 T 细胞(Th)2 极化中起着关键作用。维生素 D(VitD)参与调节许多免疫反应。
本研究检验了 VitD 是否调节 DC 中 TIM4 表达的假说。
从过敏性鼻炎(AR)患者和健康受试者中采集外周血样本。从这些样本中分离出 DC,并分析 TIM4 的表达情况。
我们观察到 AR 患者血清中骨化三醇(VitD3 的活性形式)水平低于健康受试者。外周 DC 表达更高水平的 TIM4 和更低水平的 VDR。血清骨化三醇与 DC 中 TIM4 之间的数据存在负相关。在培养物中暴露 DC 于骨化三醇可增加 VDR 的表达。我们还发现 VDR 与 DC 中 TIM4 启动子位点结合,从而抑制 TIM4 基因转录和表达。
VitD 缺乏可能通过增加 TIM4 的表达而导致 AR 的发病机制。结果表明,在治疗 AR 时,有必要考虑调节血清骨化三醇水平和 DC 中 VDR 的表达。