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Journal Articles Science Year : 2019

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

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Emma Persson
  • Function : Author
Ines Heyndrickx
  • Function : Author
Elien Gevaert
  • Function : Author
Helena Aegerter
  • Function : Author
Claus Bachert
Amanda Gonçalves
  • Function : Author
Hanne van Gorp
  • Function : Author
Hans de Haard
  • Function : Author
Christophe Blanchetot
  • Function : Author
Michael Saunders
  • Function : Author

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.
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Dates and versions

hal-02542110 , version 1 (14-04-2020)

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Emma Persson, Kenneth Verstraete, Ines Heyndrickx, Elien Gevaert, Helena Aegerter, et al.. Protein crystallization promotes type 2 immunity and is reversible by antibody treatment. Science, 2019, 364 (6442), pp.eaaw4295. ⟨10.1126/science.aaw4295⟩. ⟨hal-02542110⟩
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