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

2019; American Association for the Advancement of Science; Volume: 364; Issue: 6442 Linguagem: Inglês

10.1126/science.aaw4295

1095-9203

Emma K. Persson, Kenneth Verstraete, Ines Heyndrickx, Elien Gevaert, Helena Aegerter, Jean-Michel Percier, Kim Deswarte, Koen H. G. Verschueren, Ann Dansercoer, Delphine Gras, Pascal Chanez, Claus Bachert, Amanda Gonçalves, Hanne Van Gorp, Hans de Haard, Christophe Blanchetot, Michael Saunders, Hamida Hammad, Savvas N. Savvides, Bart N. Lambrecht,

Immune Response and Inflammation

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