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

PLoS One. 2020 Jun 4;15(6):e0233563. doi: 10.1371/journal.pone.0233563. eCollection 2020.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aminoglutethimide / pharmacology
  • Cell Line
  • Child
  • Child, Preschool
  • Cholesterol Side-Chain Cleavage Enzyme / antagonists & inhibitors
  • Cholesterol Side-Chain Cleavage Enzyme / genetics*
  • Cholesterol Side-Chain Cleavage Enzyme / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Activation / genetics
  • Female
  • Gene Knockout Techniques
  • Humans
  • Interleukin-13 / biosynthesis*
  • Lymphocyte Activation
  • Male
  • Peanut Hypersensitivity / blood
  • Peanut Hypersensitivity / immunology*
  • RNA, Messenger / genetics
  • Th2 Cells / immunology*
  • Transfection
  • Young Adult

Substances

  • IL13 protein, human
  • Interleukin-13
  • RNA, Messenger
  • Aminoglutethimide
  • Cholesterol Side-Chain Cleavage Enzyme

Grants and funding

This work was supported by NIH grant AI-77609 (to EWG), Colorado Advanced Industries Grant (to MW), Eugene F. and Easton M. Crawford Charitable Lead Unitrust (to EWG), and the Dreiseszun Fund (to EWG).