Exploiting Inhibitory Siglecs to Combat Food Allergies
Technical Report,30 Sep 2016,29 Sep 2017
University of North Carolina at Chapel Hill Chapel Hill United States
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During this first year of the award, we were able to produce important data, develop a new tool to track allergen-specific B cells, and generate two humanized mouse models. We demonstrated that Ah2 STALs targeting CD22 on B cells can prevent IgE production and allergic reactions with only a single injection in mice. We also demonstrated that Ah2 STALs targeting CD33 on human mast cells and basophils can prevent degranulation in cell culture experiments. A novel tool, Ah2 tetramer, was produced to quantify numbers of allergen-specific B cells in mice. A model to test Ah2 STALs as a therapy was developed in which nave mice were adoptively transferred memory B and T cells from peanut allergic mice. The resulting mice make robust levels of Ah2-IgE and experience anaphylaxis upon challenge. This model will be used to test STALs as a therapy to deplete memory B cells. Furthermore, two novel transgenic mouse models were generated, one expresses human CD22 on B cells and the other expresses human CD33 on mast cells. These models are vital to our proposed research.
- Medicine and Medical Research
- Food, Food Service and Nutrition