Aryl Hydrocarbon Receptor Activation and the Prevention of Type 1 Diabetes Public Deposited

http://ir.library.oregonstate.edu/concern/undergraduate_thesis_or_projects/cv43nz70p

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  • The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is an important regulator of immune responses in various disease models. In the non-obese diabetic (NOD) mouse model of type 1 diabetes, activation of this receptor leads to suppression of the autoimmune response and limits immune cell infiltration of the pancreas, stopping disease progression. It has been shown that the non-toxic compound Cl-BBQ (10- and 11-chloro- 7H- benzimidazo[2,1-a]benzo[de]Iso- quinolin-7- one) is capable of activating AhR in NOD mice. Ongoing efforts in the laboratory aim to establish how Cl-BBQ leads to immune suppression and subsequent prevention of diabetes. The goal of my project was to confirm that Cl-BBQ’s immunosuppressive capabilities are mediated through the AhR. This was accomplished by utilizing NOD.AhR.KO mice to confirm their functional ablation of AhR and to investigate the degree of islet infiltration in the pancreas following treatment with Cl-BBQ. We found that the NOD.AhR.KO mice were functionally deficient of AhR, and that AhR is required for Cl-BBQ to be effective at preventing pancreatic islet infiltration. This highlights the AhR as a therapeutic target and Cl-BBQ as a potential drug for the treatment of type 1 diabetes.
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