Protein crystallization promotes type 2 immunity and is reversible by antibody treatment-Reference-Cited by-同舟云学术

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

Published:2019-05-24 Issue:6442 Volume:364 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Persson Emma K.¹²^ORCID,Verstraete Kenneth³⁴^ORCID,Heyndrickx Ines¹²^ORCID,Gevaert Elien⁵^ORCID,Aegerter Helena¹²^ORCID,Percier Jean-Michel⁶,Deswarte Kim¹²,Verschueren Koen H. G.³⁴^ORCID,Dansercoer Ann³⁴,Gras Delphine⁷^ORCID,Chanez Pascal⁷⁸^ORCID,Bachert Claus⁵⁹,Gonçalves Amanda¹⁰¹¹^ORCID,Van Gorp Hanne¹²,De Haard Hans⁶,Blanchetot Christophe⁶,Saunders Michael⁶,Hammad Hamida¹²,Savvides Savvas N.³⁴^ORCID,Lambrecht Bart N.¹²¹²

Affiliation:

1. Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belgium.

2. Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.

3. Unit for Structural Biology, VIB Center for Inflammation Research, Ghent, Belgium.

4. Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.

5. Upper Airways Research Laboratory, ENT Department, Ghent University Hospital, Ghent, Belgium.

6. arGEN-X, Ghent, Belgium.

7. Aix Marseille University, INSERM, INRA, C2VN, Marseille, France.

8. Clinique des Bronches, Allergies et Sommeil, Hôpital Nord, AP-HM, Marseille, France.

9. Division of ENT Diseases, CLINTEC, Karolinska Institute, Stockholm, Sweden.

10. BioImaging Core, VIB Inflammation Research Center, Ghent, Belgium.

11. Department of Biomedical Molecular Biology, Ghent University, Belgium.

12. Department of Pulmonary Medicine, ErasmusMC, Rotterdam, Netherlands.

Abstract

A crystal-clear ingredient for allergy? Charcot-Leyden crystals (CLCs) are formed from the eosinophil granule protein galectin-10 (Gal10) and found in severe eosinophil-associated diseases like asthma and chronic rhinosinusitis. Whether CLCs actively contribute to disease pathogenesis is unknown. Persson et al. found that lab-grown Gal10 crystals are biosimilar to CLCs (see the Perspective by Allen and Sutherland). When given to mice, the crystals acted as a type 2 adjuvant, mimicking many of the features of human asthma. In contrast, a Gal10 mutein unable to crystallize had no effect. Antibodies against epitopes crucial for Gal10 autocrystallization could dissolve both in vitro–generated Gal10 crystals and patient-derived CLCs. Furthermore, these anti-Gal10 antibodies reversed the effects of Gal10 crystals in a humanized mouse model of asthma, suggesting a potential therapeutic approach for crystallopathies more broadly. Science , this issue p. eaaw4295 ; see also p. 738

Funder

European Research Council

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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