Allergy Project
Program for Medical Innovations
A chemical compound that selectively induces suppression of total
IgE production has been developed. This compound carries an α-GalCer analog, RCAI-X, and selectively targets marginal B cells (MZB), but not DCs or macrophages. These B cells, after taking
up the compound, express IgE mRNA, IL-21 receptor, and CXCL16 to recruit NKT cells. The NKT cells activated by RCAI-X presented
by the MZB cells produce IL-21. The NKT cell production of IL-21 in turn acts on these MZB cells to induce phosphorylation of Bmf, causing it to detach from the dynein light chain and bind with Bcl-2,
inhibiting its function and inducing apoptosis of the IgE B cells.
Bmf expression in IgG B cells is very low, therefore, the compound
only affects IgE B cells and not IgG B cells. The RCAI-X compound,
even at doses in the 1-100 ng/kg ranges, resulted in significant suppression
of not only the antigen-specific secondary IgE but also of
total IgE production (Fig.). A contract with a pharmaceutical company
(Kaken Pharmaceutical Co. Ltd.) was completed in 2013 to
develop a drug applicable for asthma, pollinosis or food allergy.
The project is supported by the RIKEN Drug Discovery and Medical
Technology Platforms and the Scientific Research Fund from
Health and Welfare.