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Journal articles
Protein crystallization promotes type 2 immunity and is reversible by antibody treatment
Emma Persson
Kenneth Verstraete
1
Ines Heyndrickx
Elien Gevaert
Helena Aegerter
Jean-Michel Percier
2
Kim Deswarte
3
Koen Verschueren
4
Ann Dansercoer
1
Delphine Gras
5
Pascal Chanez
5
Claus Bachert
6
Amanda Gonçalves
Hanne van Gorp
Hans de Haard
Christophe Blanchetot
Michael Saunders
Hamida Hammad
3
Savvas Savvides
7
Bart Lambrecht
8
Ann Dansercoer 1
Author
Delphine Gras 5
Author
Pascal Chanez 5
Author Employer institution : Aix Marseille Université
Claus Bachert 6
Author
1
Laboratory for Protein Biochemistry and Biomolecular Engineering, Department of Biochemistry, Physiology and Microbiology (K.L.-Ledeganckstraat 35 9000, GHENT - Belgium)
- UGENT - Ghent University [Belgium] (St. Pietersnieuwstraat 33, 9000 Gent, - Belgium)
2
CRCNA - Centre de Recherche en Cancérologie Nantes-Angers (France)
- CHU Angers - Centre Hospitalier Universitaire d'Angers (4 rue Larrey - 49933 Angers cedex 9 - France)
- Hôtel-Dieu de Nantes (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale (101, rue de Tolbiac, 75013 Paris - France)
- Hôpital Laennec (France)
- CNRS - Centre National de la Recherche Scientifique (France)
- Faculté de Médecine d'Angers (Rue Haute de Reculée 49045 Angers - France)
- CHU Nantes - Centre hospitalier universitaire de Nantes (1 Place Alexis-Ricordeau, 44000 Nantes - France)
3
VIB Inflammation Research Center [Ghent, Belgium] (Ghent 9052 - Belgium)
4
Unit for Structural Biology (Belgium)
- IRC - VIB-UGent Center for Inflammation Research [Gand, Belgique] (UGent-VIB Research Building FSVM, Technologiepark 71, 9052 GENT, BELGIUM - Belgium)
- VIB [Belgium] (VIB Headquarters, Rijvisschestraat 120, 9052 Gent, Belgium - Belgium)
5
C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (Faculté de Médecine de la Timone 27 boulevard Jean Moulin 13385 MARSEILLE CEDEX 5 - France)
- AMU - Aix Marseille Université : UMR_S1263 (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : UMR_S1263 (101, rue de Tolbiac, 75013 Paris - France)
- INRAE - Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement : UMR1260 (France)
6
Ghent University Hospital (De Pintelaan 185, 9000 Gent, Belgium - Belgium)
7
Unit for Structural Biology (Belgium)
- IRC - VIB-UGent Center for Inflammation Research [Gand, Belgique] (UGent-VIB Research Building FSVM, Technologiepark 71, 9052 GENT, BELGIUM - Belgium)
- VIB [Belgium] (VIB Headquarters, Rijvisschestraat 120, 9052 Gent, Belgium - Belgium)
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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Journal articles
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https://hal-amu.archives-ouvertes.fr/hal-02542110
Contributor : Annick Prémilleux <>
Submitted on : Tuesday, April 14, 2020 - 2:32:44 PM
Last modification on : Friday, December 4, 2020 - 3:09:38 AM
Contributor : Annick Prémilleux <>
Submitted on : Tuesday, April 14, 2020 - 2:32:44 PM
Last modification on : Friday, December 4, 2020 - 3:09:38 AM
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- HAL Id : hal-02542110, version 1
- DOI : 10.1126/science.aaw4295
- PRODINRA : 474730
- PUBMED : 31123109
- WOS : 000469296000035
Citation
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, American Association for the Advancement of Science, 2019, 364 (6442), pp.eaaw4295. ⟨10.1126/science.aaw4295⟩. ⟨hal-02542110⟩
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