DeKrey laboratory
Our research explores the areas of immunology and pharmacology with the applied goal of improving human and animal health. Our current efforts attempt to understand the benefits and risks of activating the aryl hydrocarbon receptor (AhR). The AhR is a required regulatory factor for development and function of the immune system. The AhR can be activated by a large number of compounds found in the environment such as foods and drugs, as well as some chemicals produced within our own bodies. This means that the AhR functions as a sensor to detect changes in both the external and the internal environment. Precise activation may serve as a therapy for some immune-mediated diseases. Unfortunately, too much or too little activation can lead to disease.
Altered mucosal antibody responses
IgA represents about 70% of all the antibody produced. It is secreted from the body across mucosal barriers (along with smaller amounts of other antibody isotypes) to act as a first line of defense against toxins and infectious agents. IgA also aids in regulating populations of microbiota in the gut and tolerance to environmental antigens. Dysregulation of IgA has been associated with a number of chronic diseases. Activation of the AhR alters antibody responses, but the overall result differs with the body compartment examined. The mechanisms responsible for these differential effects are poorly understood. Explaining the mechanisms for AhR-mediated IgA dysregulation is a focus of our work.
Enhanced resistance to Leishmania major infection
Leishmania major is an intracellular protozoan parasite of humans and other animals. Resistance to L. major infection typically depends on development of a Th1-type of cellular immune response. Activation of the AhR enhances resistance to L. major infection while simultaneously suppressing the cellular immune response. Explaining the mechanisms underlying this paradoxical observation is a focus of our work with a goal of identifying novel targets for treatment of this disease.
