Protein crystallization promotes type 2 immunity and is reversible by antibody treatment.
Adaptive Immunity
/ drug effects
Adjuvants, Immunologic
/ administration & dosage
Animals
Asthma
/ immunology
Bronchial Hyperreactivity
/ immunology
Crystallization
Disease Models, Animal
Glycoproteins
/ administration & dosage
Goblet Cells
/ immunology
Humans
Immunity, Innate
/ drug effects
Immunodominant Epitopes
/ immunology
Immunoglobulin E
/ immunology
Lysophospholipase
/ administration & dosage
Metaplasia
Mice
Mice, Inbred C57BL
Mucus
/ immunology
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
24 05 2019
24 05 2019
Historique:
received:
19
12
2018
accepted:
05
04
2019
entrez:
25
5
2019
pubmed:
28
5
2019
medline:
18
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31123109
pii: 364/6442/eaaw4295
doi: 10.1126/science.aaw4295
pii:
doi:
Substances chimiques
Adjuvants, Immunologic
0
Glycoproteins
0
Immunodominant Epitopes
0
Immunoglobulin E
37341-29-0
Lysophospholipase
EC 3.1.1.5
lysolecithin acylhydrolase
EC 3.1.1.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.