CD33 recruitment inhibits IgE-mediated anaphylaxis and desensitizes mast cells to allergen

被引:81
|
作者
Duan, Shiteng [1 ]
Koziol-White, Cynthia J. [2 ]
Jester, William F., Jr. [2 ]
Nycholat, Corwin M. [1 ]
Macauley, Matthew S. [1 ]
Panettieri, Reynold A., Jr. [2 ]
Paulson, James C. [1 ]
机构
[1] Scripps Res Inst, Dept Mol Med, La Jolla, CA USA
[2] Rutgers State Univ, Rutgers Inst Translat Med & Sci, New Brunswick, NJ USA
来源
JOURNAL OF CLINICAL INVESTIGATION | 2019年 / 129卷 / 03期
关键词
FUSION PROTEIN; FOOD ALLERGY; B-CELLS; RECEPTOR; ANTIGEN; SIGLECS; CD22; ACTIVATION; LIGANDS; IMMUNOTHERAPY;
D O I
10.1172/JCI125456
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:1387 / 1401
页数:15
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