Expression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children
| Autor: | Carah B. Santos, Vijaya Knight, Bruce J. Lanser, Erwin W. Gelfand, Shigeru Ashino, Meiqin Wang, Matthew Strand, Jordan K. Abbott, Krešo Bendelja, Elizabeth A. Esterl, Jennifer Fish |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Physiology medicine.medical_treatment Gene Expression Lymphocyte Activation White Blood Cells Families Gene Knockout Techniques 0302 clinical medicine Animal Cells Immune Physiology Allergies Gene expression Medicine and Health Sciences Child Children chemistry.chemical_classification Innate Immune System Interleukin-13 Multidisciplinary Allergic Diseases T Cells Chemistry Transfection Aminoglutethimide Cytokine medicine.anatomical_structure Child Preschool 030220 oncology & carcinogenesis Interleukin 13 Medicine Cytokines Female Cellular Types Research Article medicine.drug endocrine system medicine.medical_specialty Adolescent Science Immune Cells T cell Immunology Food Allergies Research and Analysis Methods Cell Line Young Adult 03 medical and health sciences Th2 Cells Diagnostic Medicine Internal medicine Genetics medicine Humans Peanut Hypersensitivity Cholesterol Side-Chain Cleavage Enzyme RNA Messenger Molecular Biology Techniques Molecular Biology Skin Tests Blood Cells Cholesterol side-chain cleavage enzyme Biology and Life Sciences Cell Biology Molecular Development Enzyme Activation 030104 developmental biology Enzyme Endocrinology Age Groups Immune System People and Places Clinical Immunology Population Groupings Clinical Medicine Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 6, p e0233563 (2020) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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