The aryl hydrocarbon receptor regulates an essential transcriptional element in the immunoglobulin heavy chain gene

Cellular Immunology
Michael J Wourms, Courtney E W Sulentic

Abstract

Ig heavy chain (Igh) transcription involves several regulatory elements including the 3'Igh regulatory region (3'IghRR). 3'IghRR activity is modulated by several transcription factors, including NF-κB and AP-1 and potentially the aryl hydrocarbon receptor (AhR). The prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits antibody secretion and 3'IghRR activity. However, the exact mechanism is unknown and TCDD can modulate NF-κB and AP-1 in an AhR-independent manner. To determine if the AhR is a significant regulator of the 3'IghRR, we utilized a mouse B-cell line that stably expresses a 3'IghRR-regulated transgene and either an AhR antagonist or shRNA targeting the AhR. Disruption of the AhR pathway reversed TCDD-induced suppression of the 3'IghRR-regulated transgene and of endogenous Ig demonstrating a biologically significant effect of the AhR on 3'IghRR activation. Altered human 3'IGHRR activity by AhR ligands, which include dietary, environmental, and pharmaceutical chemicals, may have significant implications to human diseases previously associated with the 3'IGHRR.

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Citations

Sep 18, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Richard L Salisbury, Courtney E W Sulentic
Jan 12, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·M GargaroF Fallarino
Aug 25, 2018·Journal of Internal Medicine·S DadvarJ L Ruas
May 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ji-Woo KimHan-Jin Park

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