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

Emma K Persson^#^{1

2}, Kenneth Verstraete^#^{3

4}, Ines Heyndrickx^#^{1

2}, Elien Gevaert⁵, Helena Aegerter^{1

2}, Jean-Michel Percier⁶, Kim Deswarte^{1

2}, Koen H G Verschueren^{3

4}, Ann Dansercoer^{3

4}, Delphine Gras⁷, Pascal Chanez^{7

8}, Claus Bachert^{5

9}, Amanda Gonçalves^{10

11}, Hanne Van Gorp^{1

2}, Hans De Haard⁶, Christophe Blanchetot⁶, Michael Saunders⁶, Hamida Hammad^{1

2}, Savvas N Savvides^{12

4}, Bart N Lambrecht^{13

2

14}

Affiliations

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 Unit for Structural Biology, VIB Center for Inflammation Research, Ghent, Belgium. bart.lambrecht@ugent.be savvas.savvides@ugent.be.
¹³ Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belgium. bart.lambrecht@ugent.be savvas.savvides@ugent.be.
¹⁴ Department of Pulmonary Medicine, ErasmusMC, Rotterdam, Netherlands.

^# Contributed equally.

PMID: 31123109
DOI: 10.1126/science.aaw4295

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

Emma K Persson et al. Science. 2019.

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

doi: 10.1126/science.aaw4295.

Authors

Affiliations

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 Unit for Structural Biology, VIB Center for Inflammation Research, Ghent, Belgium. bart.lambrecht@ugent.be savvas.savvides@ugent.be.
¹³ Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belgium. bart.lambrecht@ugent.be savvas.savvides@ugent.be.
¹⁴ Department of Pulmonary Medicine, ErasmusMC, Rotterdam, Netherlands.

^# Contributed equally.

PMID: 31123109
DOI: 10.1126/science.aaw4295

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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Comment in

Crystal-clear treatment for allergic disease.
Allen JE, Sutherland TE. Allen JE, et al. Science. 2019 May 24;364(6442):738-739. doi: 10.1126/science.aax6175. Science. 2019. PMID: 31123126 No abstract available.
Crystal cutters for blocked airways.
Bordon Y. Bordon Y. Nat Rev Immunol. 2019 Jul;19(7):412-413. doi: 10.1038/s41577-019-0187-7. Nat Rev Immunol. 2019. PMID: 31182857 No abstract available.
Making Asthma Crystal Clear.
Fahy JV, Locksley RM. Fahy JV, et al. N Engl J Med. 2019 Aug 29;381(9):882-884. doi: 10.1056/NEJMcibr1908064. N Engl J Med. 2019. PMID: 31461600 No abstract available.
Wiping Out Wheezing: Novel Therapeutic Targets for Patients with Severe Asthma.
Ramonell RP, Runnstrom MC, Yang P, Schulman DA, Lee FE. Ramonell RP, et al. Am J Respir Crit Care Med. 2020 Dec 1;202(11):1576-1578. doi: 10.1164/rccm.202005-1797RR. Am J Respir Crit Care Med. 2020. PMID: 33052701 No abstract available.

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

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

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