Research Projects

Peter R. Hoffmann, Ph.D.
Department of Cell and Molecular Biology
John A. Burns School of Medicine

Dr. Hoffmann and Ann Hashimoto, Animal Technician.

FuKun Hoffmann, Lab Technician

Kai Thiemann, a German exchange student also working in the Hoffmann lab.

The research interests of our laboratory involve the effects of dietary selenium (Se) on immune responses, such as those that drive allergic asthma. Dietary Se is a potent antioxidant that carries out its biological functions through the actions of selenoproteins, and there are 25 selenoproteins in humans that exhibit a wide variety of functions. We have written reviews describing the influences of Se and selenproteins on immune responses (1, 2). Interestingly, more than half of the selenoproteins have no function that has been identified. Thus, a major of our laboratory involves elucidating functions of specific selenoproteins for which no function has yet been identified.

Our laboratory has used a mouse model of asthma to investigate the effects of dietary Se on the development of asthma. In particular, standard C57BL/6 mice maintained on diets with low (0.08 ppm), medium (0.25 ppm), or high (2.7 ppm) levels of Se were subjected to intra-nasal challenges with ovalbumin (OVA). The mice were evaluated using several different parameters for severity of allergic asthma and results demonstrated that mice fed low Se diets had low levels of asthma, while mice fed medium levels of Se had the highest levels of asthma (Fig. 1). Surprisingly, increasing Se in the diet from medium to high levels lowered the levels of asthma. These findings were published in the Journal of Immunology (3). These data have led to a new perspective on the relationship between Se and asthma, which we have published in the journal Allergy (4). In general, we believe Se levels have profound effects on the T helper cells that drive asthma and these effects, together with the influence on lung oxidative stress, play a major role in modulating the development of asthma in humans (Fig 2).

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Figure 1.

Figure 2.

We have conducted subsequent studies that have established new approaches to analyzing inflammation in the lungs of mice during asthma (5). Our intentions are to use these new approaches and other techniques to determine mechanisms by which T helper cells are affected by dietary Se. In particular, we have new data that suggest Se intake affects the proliferation and differentiation of T helper cells through specific signaling cascades. Our future studies will focus on defining these effects and identifying individual selenoproteins involved in mediating these effects. For example, we have been evaluating the role of selenoprotein K (sel K), one of the selenoproteins of unknown function. Our preliminary data suggest sel K is expressed in the endoplasmic reticulum (ER) in a variety of leukocytes including monocytes/macrophages, as well as T and B cells (Fig. 3). In addition, sel K is detected in lymphoid tissues in mice (Fig. 4) and we are in the process of developing a sel K knockout mouse model. Our future studies will determine how sel K and other selenoproteins function to mediate the effects of dietary Se on immune responses such as those that drive allergic asthma.

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Figure 3.

Figure 4.