Activation of aryl hydrocarbon receptor with structurally diverse ligands represses class switch to immunoglobulin A
| Autor: | Alex B Costa, Aspen L Hirsch, Gregory K DeKrey |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 202:188.17-188.17 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.202.supp.188.17 |
| Popis: | Activation of the aryl hydrocarbon receptor (AhR) with its prototypical agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) represses activation-induced cytidine deaminase expression and B cell class switch recombination (CSR). Structurally diverse AhR agonists have been shown to have differing impacts on T cell differentiation. We hypothesized that AhR activation with structurally diverse agonists would have differential impacts on CSR in B cells. The following agonists were tested: the endogenous ligands cinnabarinic acid (CA), 5,11-dihydroindolo[3,2-b]carbazole-6-carboxaldehyde (FICZ), and kynurenine (Kyn); the pharmaceuticals omeprazole (Omep) and tamoxifen (Tam); and the dietary component indole-3-carbanol (I3C). Mouse splenic CD19+ B cells were cultured with LPS, α-IgD-dextran, and TGF-β1 to stimulate CSR to IgA. IgA expression was measured by flow cytometry. Relative to control cells (10.84% IgA+), exposure to CA, FICZ, I3C, Kyn, Omep, Tam, or TCDD significantly decreased the proportion of IgA+ cells (P < 0.05) to 4.48%, 2.48%, 2.25%, 4.39%, 0.79%, 6.95% and 3.93%, respectively. In contrast, CH-223191, an AhR antagonist, significantly increased the proportion of IgA+ cells to 16.19%. These results suggest that repression of CSR is a common effect of AhR agonists in activated mouse B cells. |
| Databáze: | OpenAIRE |
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