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Article Dans Une Revue Science Année : 2019

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

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

Résumé

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.

Dates et versions

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

Identifiants

Citer

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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