Expression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children.
Meiqin WangMatthew J StrandBruce J LanserCarah SantosKreso BendeljaJennifer FishElizabeth A EsterlShigeru AshinoJordan K AbbottVijaya KnightErwin W GelfandPublished in: PloS one (2020)
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.
Keyphrases
- crispr cas
- young adults
- peripheral blood
- poor prognosis
- ejection fraction
- end stage renal disease
- type diabetes
- insulin resistance
- allergic rhinitis
- adipose tissue
- prognostic factors
- oxidative stress
- chronic kidney disease
- nitric oxide
- dendritic cells
- protein protein
- electronic health record
- glycemic control
- high fat diet induced
- endoplasmic reticulum stress
- patient reported