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

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 cont...

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Autores principales: Meiqin Wang, Matthew J Strand, Bruce J Lanser, Carah Santos, Kreso Bendelja, Jennifer Fish, Elizabeth A Esterl, Shigeru Ashino, Jordan K Abbott, Vijaya Knight, Erwin W Gelfand
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Publicado: Public Library of Science (PLoS) 2020
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Acceso en línea:https://doaj.org/article/9070db838c9e4d61b7a8bd0bf7c36877
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spelling oai:doaj.org-article:9070db838c9e4d61b7a8bd0bf7c368772021-12-02T20:15:51ZExpression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children.1932-620310.1371/journal.pone.0233563https://doaj.org/article/9070db838c9e4d61b7a8bd0bf7c368772020-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0233563https://doaj.org/toc/1932-6203Activation 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.Meiqin WangMatthew J StrandBruce J LanserCarah SantosKreso BendeljaJennifer FishElizabeth A EsterlShigeru AshinoJordan K AbbottVijaya KnightErwin W GelfandPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 15, Iss 6, p e0233563 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Meiqin Wang
Matthew J Strand
Bruce J Lanser
Carah Santos
Kreso Bendelja
Jennifer Fish
Elizabeth A Esterl
Shigeru Ashino
Jordan K Abbott
Vijaya Knight
Erwin W Gelfand
Expression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children.
description 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.
format article
author Meiqin Wang
Matthew J Strand
Bruce J Lanser
Carah Santos
Kreso Bendelja
Jennifer Fish
Elizabeth A Esterl
Shigeru Ashino
Jordan K Abbott
Vijaya Knight
Erwin W Gelfand
author_facet Meiqin Wang
Matthew J Strand
Bruce J Lanser
Carah Santos
Kreso Bendelja
Jennifer Fish
Elizabeth A Esterl
Shigeru Ashino
Jordan K Abbott
Vijaya Knight
Erwin W Gelfand
author_sort Meiqin Wang
title Expression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children.
title_short Expression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children.
title_full Expression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children.
title_fullStr Expression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children.
title_full_unstemmed Expression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children.
title_sort expression and activation of the steroidogenic enzyme cyp11a1 is associated with il-13 production in t cells from peanut allergic children.
publisher Public Library of Science (PLoS)
publishDate 2020
url https://doaj.org/article/9070db838c9e4d61b7a8bd0bf7c36877
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