Autor: |
Nguyen, Nikki Lynn Hue, Chen, Kong, Mcaleer, Jeremy, Kolls, Jay K. |
Zdroj: |
Infection and Immunity; February 2013, Vol. 81 Issue: 5 p1510-1519, 10p |
Abstrakt: |
ABSTRACTOX40 ligand (OX40L) is a costimulatory molecule involved in Th2 allergic responses. It has been shown that vitamin D deficiency is associated with increased OX40L expression in peripheral CD11c+cells and controls Th2 responses to Aspergillus fumigatusin vitroin cystic fibrosis (CF) patients with allergic bronchopulmonary aspergillosis (ABPA). To investigate if vitamin D deficiency regulated OX40L and Th2 responses in vivo, we examined the effect of nutritional vitamin D deficiency on costimulatory molecules in CD11c+cells and A. fumigatus-induced Th2 responses. Vitamin D-deficient mice showed increased expression of OX40L on lung CD11c+cells, and OX40L was critical for enhanced Th2 responses to A. fumigatusin vivo. In in vitroassays, vitamin D treatment led to vitamin D receptor (VDR) binding in the promoter region of OX40L and significantly decreased the promoter activity of the OX40L promoter. In addition, vitamin D altered NF-?B p50 binding in the OX40L promoter that may be responsible for repression of OX40L expression. These data show that vitamin D can act directly on OX40L, which impacts Th2 responses and supports the therapeutic use of vitamin D in diseases regulated by OX40L. |
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