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SUMMARY:EU Life Lecture -  Spontaneous protein crystallization as a driver
  of immunity  - Prof. Bart Lambrecht\; VIB\, Belgium
DTSTART:20191203T140000Z
DTEND:20191203T150000Z
UID:TALK125251@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:Spontaneous protein crystallization is a rare event in vivo\, 
 yet Charcot-Leyden crystals (CLC) consisting of\nthe protein galectin-10 (
 Gal10) are frequently observed in eosinophilic diseases like asthma. It is
  unclear\nif they exacerbate disease. Release of Gal10 and extracellular c
 rystallization was associated with EEtosis\nof eosinophils in human primar
 y eosinophils. We found that recombinant crystalline Gal10 was\ncompletely
  biosimilar to in vivo obtained CLCs and induced innate airway inflammatio
 n\, whereas a soluble\nGal10 engineered to resist crystallization was iner
 t in the airways. When co-administered with harmless\nantigens\, only crys
 talline Gal10 stimulated adaptive immunity\, Th2 sensitization\, goblet ce
 ll metaplasia\nand airway eosinophilia. Transgenic mice engineered to over
 express human Gal10 in eosinophils (GALILEO\nmice) had enhanced features o
 f asthma including mucus plugging and bronchial hyperreactivity. To probe\
 nfor the drugability of this pathway\, we generated a panel of antibodies.
  Antibodies directed against key\nepitopes of the crystallization interfac
 e dissolved pre-existing CLC in patient-derived mucus within hours\,\nand 
 reversed crystal driven inflammation\, goblet cell metaplasia\, IgE synthe
 sis and bronchial\nhyperreactivity in a humanized asthma model. Thus\, gal
 ectin10 and CLC promote key features of asthma\nand can be targeted by cry
 stal dissolving antibodies.
LOCATION:Babraham - The Cambridge Building - Petersfield Lecture Theatre
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