Exploiting Inhibitory Siglecs to Combat Food Allergies
Technical Report,30 Sep 2017,29 Sep 2018
University of North Carolina at Chapel Hill Chapel Hill United States
Pagination or Media Count:
During the second year of this award, we have continued to generate important data related to targeting of CD22 on B cells and CD33 on mast cells to abrogate food allergies. We have developed a new model using adoptive transfer of peanut allergic splenocytes into nave mice to evaluate depletion of memory B cells in an allergen-specific fashion. We have demonstrated that Ara h 2 STALs targeting CD22 can indeed deplete Ara h 2-specific B cells via IgE and anaphylactic measurements. The tolerance induced by Ara h 2 STALs is long-lasting. We are now poised to evaluate this approach in the humanized CD22mouse model that we developed last reporting period, along with utilizing human B cells in an assay under development. In terms of targeting CD33 in this past year, we have used the transgenic mouse model with human CD33 expressed on mast cells to evaluate the activity of CD33 ligand CD33L STALs on allergen-mediated activation of mast cells in vitro and in vivo. In particular we found that CD33L-STALs profoundly suppress allergen mediated degranulation of bone marrow derived mast cells in vitro and prevent anaphylaxis in mouse models of passive cutaneous and passive systemic anaphylaxis. Animals remain desensitized to subsequent antigen challenge. The results offer promise for developing therapies for patients with allergies and allergic asthma to desensitize mast cells and improve approaches for inducing tolerance to the offending antigens.
- Medicine and Medical Research