Protein crystallization promotes type 2 immunity and is reversible by antibody treatment - PubMed (original) (raw)

. 2019 May 24;364(6442):eaaw4295.

doi: 10.1126/science.aaw4295.

Kenneth Verstraete # 3 4, Ines Heyndrickx # 1 2, Elien Gevaert 5, Helena Aegerter 1 2, Jean-Michel Percier 6, Kim Deswarte 1 2, Koen H G Verschueren 3 4, Ann Dansercoer 3 4, Delphine Gras 7, Pascal Chanez 7 8, Claus Bachert 5 9, Amanda Gonçalves 10 11, Hanne Van Gorp 1 2, Hans De Haard 6, Christophe Blanchetot 6, Michael Saunders 6, Hamida Hammad 1 2, Savvas N Savvides 12 4, Bart N Lambrecht 13 2 14

Affiliations

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

Emma K Persson et al. Science. 2019.

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.

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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