Advanced search
1 file | 4.78 MB

Protein crystallization promotes type 2 immunity and is reversible by antibody treatment

(2019) SCIENCE. 364(6442).
Author
Organization
Abstract
Although spontaneous protein crystallization is a rare event in vivo, Charcot-Leyden crystals (CLCs) consisting of galectin-10 (Gal10) protein are frequently observed in eosinophilic diseases, such as asthma. We found that CLCs derived from patients showed crystal packing and Gal10 structure identical to those of Gal10 crystals grown in vitro. When administered to the airways, crystalline Gal10 stimulated innate and adaptive immunity and acted as a type 2 adjuvant. By contrast, a soluble Gal10 mutein was inert. Antibodies directed against key epitopes of the CLC crystallization interface dissolved preexisting CLCs in patient-derived mucus within hours and reversed crystal-driven inflammation, goblet-cell metaplasia, immunoglobulin E (IgE) synthesis, and bronchial hyperreactivity (BHR) in a humanized mouse model of asthma. Thus, protein crystals may promote hallmark features of asthma and are targetable by crystal-dissolving antibodies.
Keywords
LEYDEN CRYSTAL PROTEIN, MAJOR BASIC-PROTEIN, EOSINOPHIL, LYSOPHOSPHOLIPASE, BIOCHEMICAL-CHARACTERIZATION, URIC-ACID, INFLAMMATION, ASTHMA, GALECTIN-10, MODEL, ACTIVATION

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 4.78 MB

Citation

Please use this url to cite or link to this publication:

Chicago
Persson, Emma, Kenneth Verstraete, Ines Heyndrickx, Elien Gevaert, Helena Catharine Aegerter, Jean-Michel Percier, Kim Deswarte, et al. 2019. “Protein Crystallization Promotes Type 2 Immunity and Is Reversible by Antibody Treatment.” Science 364 (6442).
APA
Persson, E., Verstraete, K., Heyndrickx, I., Gevaert, E., Aegerter, H. C., Percier, J.-M., Deswarte, K., et al. (2019). Protein crystallization promotes type 2 immunity and is reversible by antibody treatment. SCIENCE, 364(6442).
Vancouver
1.
Persson E, Verstraete K, Heyndrickx I, Gevaert E, Aegerter HC, Percier J-M, et al. Protein crystallization promotes type 2 immunity and is reversible by antibody treatment. SCIENCE. 2019;364(6442).
MLA
Persson, Emma et al. “Protein Crystallization Promotes Type 2 Immunity and Is Reversible by Antibody Treatment.” SCIENCE 364.6442 (2019): n. pag. Print.
@article{8619543,
  abstract     = {Although spontaneous protein crystallization is a rare event in vivo, Charcot-Leyden crystals (CLCs) consisting of galectin-10 (Gal10) protein are frequently observed in eosinophilic diseases, such as asthma. We found that CLCs derived from patients showed crystal packing and Gal10 structure identical to those of Gal10 crystals grown in vitro. When administered to the airways, crystalline Gal10 stimulated innate and adaptive immunity and acted as a type 2 adjuvant. By contrast, a soluble Gal10 mutein was inert. Antibodies directed against key epitopes of the CLC crystallization interface dissolved preexisting CLCs in patient-derived mucus within hours and reversed crystal-driven inflammation, goblet-cell metaplasia, immunoglobulin E (IgE) synthesis, and bronchial hyperreactivity (BHR) in a humanized mouse model of asthma. Thus, protein crystals may promote hallmark features of asthma and are targetable by crystal-dissolving antibodies.},
  articleno    = {751},
  author       = {Persson, Emma and Verstraete, Kenneth and Heyndrickx, Ines and Gevaert, Elien and Aegerter, Helena Catharine and Percier, Jean-Michel and Deswarte, Kim and Verschueren, Koen and Dansercoer, Ann and Gras, Delphine and Chanez, Pascal and Bachert, Claus and Gonçalves, Amanda and Van Gorp, Hanne and De Haard, Hans and Blanchetot, Christophe and Saunders, Michael and Hammad, Hamida and Savvides, Savvas and Lambrecht, Bart},
  issn         = {0036-8075},
  journal      = {SCIENCE},
  keywords     = {LEYDEN CRYSTAL PROTEIN,MAJOR BASIC-PROTEIN,EOSINOPHIL,LYSOPHOSPHOLIPASE,BIOCHEMICAL-CHARACTERIZATION,URIC-ACID,INFLAMMATION,ASTHMA,GALECTIN-10,MODEL,ACTIVATION},
  language     = {eng},
  number       = {6442},
  pages        = {17},
  title        = {Protein crystallization promotes type 2 immunity and is reversible by antibody treatment},
  url          = {http://dx.doi.org/10.1126/science.aaw4295},
  volume       = {364},
  year         = {2019},
}

Altmetric
View in Altmetric
Web of Science
Times cited: