title: Vitamin D regulation of OX40 ligand in immune responses to Aspergillus fumigatus.
abstract: OX40 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 fumigatus in vitro in 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. fumigatus in vivo. In in vitro assays, 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-κB 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.
authors: Department of Genetics, Louisiana State University Health Sciences Center (LSUHSC), New Orleans, Louisiana, USA.
authors: Nikki Lynn Hue
authors: NL
authors: Nguyen
authors: Kong
authors: K
authors: Chen
authors: Jeremy
authors: J
authors: McAleer
authors: Jay K
authors: JK
authors: Kolls
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001228:Aspergillosis / Q000276:immunology* / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000166:cytology; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D053278:OX40 Ligand / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D018167:Receptors, Calcitriol / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000378:metabolism*; D014807:Vitamin D / Q000494:pharmacology*; D014808:Vitamin D Deficiency / Q000276:immunology* / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D008562:Membrane Glycoproteins; D052002:NF-kappa B p50 Subunit; D053278:OX40 Ligand; D018167:Receptors, Calcitriol; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; D014815:Vitamins; D014807:Vitamin D