1. Expression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children.
- Author
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Wang M, Strand MJ, Lanser BJ, Santos C, Bendelja K, Fish J, Esterl EA, Ashino S, Abbott JK, Knight V, and Gelfand EW
- Subjects
- Adolescent, Aminoglutethimide pharmacology, Cell Line, Child, Child, Preschool, Cholesterol Side-Chain Cleavage Enzyme antagonists & inhibitors, Enzyme Activation drug effects, Enzyme Activation genetics, Female, Gene Knockout Techniques, Humans, Lymphocyte Activation, Male, Peanut Hypersensitivity blood, RNA, Messenger genetics, Transfection, Young Adult, Cholesterol Side-Chain Cleavage Enzyme genetics, Cholesterol Side-Chain Cleavage Enzyme metabolism, Interleukin-13 biosynthesis, Peanut Hypersensitivity immunology, Th2 Cells immunology
- Abstract
Activation of the steroidogenic enzyme CYP11A1 was shown to be necessary for the development of peanut-induced intestinal anaphylaxis and IL-13 production in allergic mice. We determined if levels of CYP11A1 in peripheral blood T cells from peanut-allergic (PA) children compared to non-allergic controls were increased and if levels correlated to IL-13 production and oral challenge outcomes to peanut. CYP11A1 mRNA and protein levels were significantly increased in activated CD4+ T cells from PA patients. In parallel, IL-13 production was significantly increased; IFNγ levels were not different between groups. There were significant correlations between expression levels of CYP11A1 mRNA and levels of IL13 mRNA and protein, levels of serum IgE anti-Ara h 2 and to outcomes of peanut challenge. The importance of CYP11A1 on cytokine production was tested using a CYP11A1 CRISPR/Cas9 KO plasmid or an inhibitor of enzymatic CYP11A1 activity. Inhibition of CYP11A1 activation in patient cells treated with the inhibitor, aminoglutethimide, or CD4+ T cell line transfected with the CYP11A1 KO plasmid resulted in reduced IL-13 production. These data suggest that the CYP11A1-CD4+Tcell-IL-13 axis in activated CD4+ T cells from PA children is associated with development of PA reactions. CYP11A1 may represent a novel target for therapeutic intervention in PA children., Competing Interests: The authors have no conflicts of interest to declare.
- Published
- 2020
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