Biotin deficiency enhances the inflammatory response of human dendritic cells

• Published in: American Journal of Physiology: Cell Physiology Vol. 311; no. 3; pp. C386 - C391
• Main Authors: Agrawal, Sudhanshu, Agrawal, Anshu, Said, Hamid M
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.09.2016
• Subjects: Biotin - metabolism; Biotinidase Deficiency - metabolism; Biotinidase Deficiency - pathology; Cell culture; Dendritic Cells - metabolism; Dendritic Cells - pathology; Humans; Immunity (Disease); Inflammation - metabolism; Inflammation - pathology; Interferon-gamma - metabolism; Interleukin-12 Subunit p40 - metabolism; Interleukin-1beta - metabolism; Interleukin-23 - metabolism; Lipopolysaccharides - pharmacology; Lymphocyte Activation - drug effects; Lymphocyte Activation - physiology; Monocytes - metabolism; Monocytes - pathology; Physiology; Th1 Cells - drug effects; Th1 Cells - metabolism; Th1 Cells - pathology; Th17 Cells - drug effects; Th17 Cells - metabolism; Tumor Necrosis Factor-alpha - metabolism; Vitamin B; Vitamin deficiency; dendritic cells; inflammation; human; biotin
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00141.2016

The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.