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

Autori
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.

Izvornik
PLOS ONE (1932-6203) 15 (2020), 6; E0233563, 16

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
T cells, food allergies, gene expression, transfection, children, cytokines, skin tests, messenger RNA

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Kliničke medicinske znanosti, Interdisciplinarne biotehničke znanosti

POVEZANOST RADA