CD33 recruitment inhibits IgE-mediated anaphylaxis and desensitizes mast cells to allergen
Year: 2019
Type: article
Abstract: Allergen immunotherapy for patients with allergies begins with weekly escalating doses of allergen under medical supervision to monitor and treat IgE mast cell-mediated anaphylaxis. There is currently no treatment to safely desensitize mast cells to enable robust allergen immunotherapy with therapeutic levels of allergen. Here, we demonstrated that liposomal nanoparticles bearing an allergen and a high-affinity glycan ligand of the inhibitory receptor CD33 profoundly suppressed IgE-mediated activation of mast cells, prevented anaphylaxis in Tg mice with mast cells expressing human CD33, and desensitized mice to subsequent allergen challenge for several days. We showed that high levels of CD33 were consistently expressed on human skin mast cells and that the antigenic liposomes with CD33 ligand prevented IgE-mediated bronchoconstriction in slices of human lung. The results demonstrated the potential of exploiting CD33 to desensitize mast cells to provide a therapeutic window for administering allergen immunotherapy without triggering anaphylaxis.
DOI: 10.1172/jci125456
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Defense, Brown University, Vanderbilt University, Northwestern University, Vanderbilt University Medical Center, National Institutes of Health, University of North Carolina at Chapel Hill, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases
Awards: Using siglecs and their ligands to treat allergic diseases SALTAD, Exploiting inhibitory Siglecs for desensitizing mast cells, EXPLOITING INHIBITORY SIGLECS TO COMBAT FOOD ALLERGIES, G4119534169, Glycobiology of Inflammatory Lung Diseases, G5850682332, Inducing antigen specific B cell tolerance
OpenAlex ID: W2909993605