PMID- 31123109
OWN - NLM
STAT- MEDLINE
DCOM- 20191216
LR  - 20220410
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Linking)
VI  - 364
IP  - 6442
DP  - 2019 May 24
TI  - Protein crystallization promotes type 2 immunity and is reversible by antibody 
      treatment.
LID - eaaw4295 [pii]
LID - 10.1126/science.aaw4295 [doi]
AB  - 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.
CI  - Copyright (c) 2019 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Persson, Emma K
AU  - Persson EK
AUID- ORCID: 0000-0002-9874-7991
AD  - Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - Verstraete, Kenneth
AU  - Verstraete K
AUID- ORCID: 0000-0001-6544-6458
AD  - Unit for Structural Biology, VIB Center for Inflammation Research, Ghent, 
      Belgium.
AD  - Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.
FAU - Heyndrickx, Ines
AU  - Heyndrickx I
AUID- ORCID: 0000-0001-8091-6390
AD  - Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - Gevaert, Elien
AU  - Gevaert E
AUID- ORCID: 0000-0002-0992-3085
AD  - Upper Airways Research Laboratory, ENT Department, Ghent University Hospital, 
      Ghent, Belgium.
FAU - Aegerter, Helena
AU  - Aegerter H
AUID- ORCID: 0000-0002-5755-9126
AD  - Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - Percier, Jean-Michel
AU  - Percier JM
AD  - arGEN-X, Ghent, Belgium.
FAU - Deswarte, Kim
AU  - Deswarte K
AD  - Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - Verschueren, Koen H G
AU  - Verschueren KHG
AUID- ORCID: 0000-0002-3522-9169
AD  - Unit for Structural Biology, VIB Center for Inflammation Research, Ghent, 
      Belgium.
AD  - Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.
FAU - Dansercoer, Ann
AU  - Dansercoer A
AD  - Unit for Structural Biology, VIB Center for Inflammation Research, Ghent, 
      Belgium.
AD  - Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.
FAU - Gras, Delphine
AU  - Gras D
AUID- ORCID: 0000-0002-6630-2955
AD  - Aix Marseille University, INSERM, INRA, C2VN, Marseille, France.
FAU - Chanez, Pascal
AU  - Chanez P
AUID- ORCID: 0000-0003-4059-0917
AD  - Aix Marseille University, INSERM, INRA, C2VN, Marseille, France.
AD  - Clinique des Bronches, Allergies et Sommeil, Hopital Nord, AP-HM, Marseille, 
      France.
FAU - Bachert, Claus
AU  - Bachert C
AD  - Upper Airways Research Laboratory, ENT Department, Ghent University Hospital, 
      Ghent, Belgium.
AD  - Division of ENT Diseases, CLINTEC, Karolinska Institute, Stockholm, Sweden.
FAU - Goncalves, Amanda
AU  - Goncalves A
AUID- ORCID: 0000-0003-2748-3033
AD  - BioImaging Core, VIB Inflammation Research Center, Ghent, Belgium.
AD  - Department of Biomedical Molecular Biology, Ghent University, Belgium.
FAU - Van Gorp, Hanne
AU  - Van Gorp H
AD  - Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - De Haard, Hans
AU  - De Haard H
AD  - arGEN-X, Ghent, Belgium.
FAU - Blanchetot, Christophe
AU  - Blanchetot C
AD  - arGEN-X, Ghent, Belgium.
FAU - Saunders, Michael
AU  - Saunders M
AD  - arGEN-X, Ghent, Belgium.
FAU - Hammad, Hamida
AU  - Hammad H
AD  - Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belgium.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
FAU - Savvides, Savvas N
AU  - Savvides SN
AUID- ORCID: 0000-0003-3420-5947
AD  - Unit for Structural Biology, VIB Center for Inflammation Research, Ghent, 
      Belgium. bart.lambrecht@ugent.be savvas.savvides@ugent.be.
AD  - Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.
FAU - Lambrecht, Bart N
AU  - Lambrecht BN
AD  - Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belgium. 
      bart.lambrecht@ugent.be savvas.savvides@ugent.be.
AD  - Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
AD  - Department of Pulmonary Medicine, ErasmusMC, Rotterdam, Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Glycoproteins)
RN  - 0 (Immunodominant Epitopes)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 3.1.1.5 (Lysophospholipase)
RN  - EC 3.1.1.5 (lysolecithin acylhydrolase)
SB  - IM
CIN - Science. 2019 May 24;364(6442):738-739. PMID: 31123126
CIN - Nat Rev Immunol. 2019 Jul;19(7):412-413. PMID: 31182857
CIN - N Engl J Med. 2019 Aug 29;381(9):882-884. PMID: 31461600
CIN - Am J Respir Crit Care Med. 2020 Dec 1;202(11):1576-1578. PMID: 33052701
MH  - Adaptive Immunity/*drug effects
MH  - Adjuvants, Immunologic/administration & dosage/*chemistry/*pharmacology
MH  - Animals
MH  - Asthma/immunology/pathology/*therapy
MH  - Bronchial Hyperreactivity/immunology/therapy
MH  - Crystallization
MH  - Disease Models, Animal
MH  - Glycoproteins/administration & dosage/*chemistry/immunology/*pharmacology
MH  - Goblet Cells/immunology/pathology
MH  - Humans
MH  - Immunity, Innate/*drug effects
MH  - Immunodominant Epitopes/immunology
MH  - Immunoglobulin E/immunology
MH  - Lysophospholipase/administration & dosage/*chemistry/immunology/*pharmacology
MH  - Metaplasia
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mucus/immunology
EDAT- 2019/05/28 06:00
MHDA- 2019/12/18 06:00
CRDT- 2019/05/25 06:00
PHST- 2018/12/19 00:00 [received]
PHST- 2019/04/05 00:00 [accepted]
PHST- 2019/05/25 06:00 [entrez]
PHST- 2019/05/28 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
AID - 364/6442/eaaw4295 [pii]
AID - 10.1126/science.aaw4295 [doi]
PST - ppublish
SO  - Science. 2019 May 24;364(6442):eaaw4295. doi: 10.1126/science.aaw4295.