Expression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children

• Published in: PloS one 2020-06, Vol.15 (6), p.e0233563-e0233563
• Main Authors: Wang, Meiqin, Strand, Matthew J, Lanser, Bruce J, Santos, Carah, Bendelja, Kreso, Fish, Jennifer, Esterl, Elizabeth A, Ashino, Shigeru, Abbott, Jordan K, Knight, Vijaya, Gelfand, Erwin W
• Format: Article
• Language: English
• Subjects: Aminoglutethimide; Anaphylaxis; Ara h 2 antigen; Binding sites; Biology; Biology and Life Sciences; Biomarkers; CD4 antigen; Cell activation; Children; CRISPR; Cytochrome; Cytochrome P-450; Cytokines; Development and progression; Enzymes; Food allergies; Gene expression; Health aspects; Immunoglobulin E; Immunotherapy; Inhibitors; Interleukin 1; Interleukin 13; Intestine; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Messenger RNA; mRNA; Patients; Peanut allergy; Peanuts; Pediatric food hypersensitivity; Pediatrics; People and Places; Peripheral blood; Proteins; Research and Analysis Methods; RNA; Steroids (Organic compounds); T cells; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0233563

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.sup.+ T cells from PA patients. In parallel, IL-13 production was significantly increased; IFN[gamma] 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.sup.+ T cell line transfected with the CYP11A1 KO plasmid resulted in reduced IL-13 production. These data suggest that the CYP11A1-CD4.sup.+ Tcell-IL-13 axis in activated CD4.sup.+ T cells from PA children is associated with development of PA reactions. CYP11A1 may represent a novel target for therapeutic intervention in PA children.