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IL-33trap is a novel IL-33-neutralizing biologic that inhibits allergic airway inflammation

Aurora Holgado Munoz (UGent) , Harald Braun (UGent) , Elien Van Nuffel (UGent) , Sammy Detry (UGent) , Martijn Schuijs (UGent) , Kim Deswarte (UGent) , Karl Vergote (UGent) , Mira Haegman (UGent) , Griet Baudelet (UGent) , Jurgen Haustraete (UGent) , et al.
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Abstract
Background: The emergence of IL-33 as a key molecular player in the development and propagation of widespread inflammatory diseases, including asthma and atopic dermatitis, has established the need for effective IL-33 neutralizing biologics. Objective: Here we describe the development and validation of a new antagonist of IL-33, termed IL-33trap, which combines the extracellular domains of the IL-33 receptor (ST2) and its coreceptor, IL-1 receptor accessory protein, into a single fusion protein. Methods: We produced and purified recombinant IL-33trap from human cells and analyzed its IL-33 binding affinity and IL-33 antagonistic activity in cultured cells and mice. IL-33trap activity was also benchmarked with a recombinant soluble ST2 corresponding to the naturally occurring IL-33 decoy receptor. Finally, we studied the effect of IL-33trap in the Alternaria alternata mouse model of allergic airway inflammation. Results: In vitro IL-33trap binds IL-33 and inhibits IL-33 activity to a much stronger degree than soluble ST2. Furthermore, IL-33trap inhibits eosinophil infiltration, splenomegaly, and production of signature cytokines in splenic lymphocytes and lung tissue on IL-33 injection. Finally, administration of IL-33trap at the time of allergen challenge inhibits inflammatory responses in a preclinical mouse model of acute allergic airway inflammation. Conclusions: IL-33trap is a novel IL-33 antagonist that outperforms the natural IL-33 decoy receptor and shows anti-inflammatory activities in a preclinical mouse model of acute allergic airway inflammation when administered at the time of allergen challenge.
Keywords
INNATE LYMPHOID-CELLS, TYPE-2 INFLAMMATION, SOLUBLE ST2, INTERLEUKIN 33, SEVERE ASTHMA, IDENTIFICATION, RECEPTOR, DISEASE, IMMUNOGENICITY, ASSOCIATION, IL-33, soluble ST2, antagonist, airway inflammation, allergic asthma

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Chicago
Holgado Munoz, Aurora, Harald Braun, Elien Van Nuffel, Sammy Detry, Martijn Schuijs, Kim Deswarte, Karl Vergote, et al. 2019. “IL-33trap Is a Novel IL-33-neutralizing Biologic That Inhibits Allergic Airway Inflammation.” Journal of Allergy and Clinical Immunology 144 (1): 204–215.
APA
Holgado Munoz, A., Braun, H., Van Nuffel, E., Detry, S., Schuijs, M., Deswarte, K., Vergote, K., et al. (2019). IL-33trap is a novel IL-33-neutralizing biologic that inhibits allergic airway inflammation. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 144(1), 204–215.
Vancouver
1.
Holgado Munoz A, Braun H, Van Nuffel E, Detry S, Schuijs M, Deswarte K, et al. IL-33trap is a novel IL-33-neutralizing biologic that inhibits allergic airway inflammation. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 2019;144(1):204–15.
MLA
Holgado Munoz, Aurora et al. “IL-33trap Is a Novel IL-33-neutralizing Biologic That Inhibits Allergic Airway Inflammation.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 144.1 (2019): 204–215. Print.
@article{8625638,
  abstract     = {Background: The emergence of IL-33 as a key molecular player in the development and propagation of widespread inflammatory diseases, including asthma and atopic dermatitis, has established the need for effective IL-33 neutralizing biologics. 
Objective: Here we describe the development and validation of a new antagonist of IL-33, termed IL-33trap, which combines the extracellular domains of the IL-33 receptor (ST2) and its coreceptor, IL-1 receptor accessory protein, into a single fusion protein. 
Methods: We produced and purified recombinant IL-33trap from human cells and analyzed its IL-33 binding affinity and IL-33 antagonistic activity in cultured cells and mice. IL-33trap activity was also benchmarked with a recombinant soluble ST2 corresponding to the naturally occurring IL-33 decoy receptor. Finally, we studied the effect of IL-33trap in the Alternaria alternata mouse model of allergic airway inflammation. 
Results: In vitro IL-33trap binds IL-33 and inhibits IL-33 activity to a much stronger degree than soluble ST2. Furthermore, IL-33trap inhibits eosinophil infiltration, splenomegaly, and production of signature cytokines in splenic lymphocytes and lung tissue on IL-33 injection. Finally, administration of IL-33trap at the time of allergen challenge inhibits inflammatory responses in a preclinical mouse model of acute allergic airway inflammation. 
Conclusions: IL-33trap is a novel IL-33 antagonist that outperforms the natural IL-33 decoy receptor and shows anti-inflammatory activities in a preclinical mouse model of acute allergic airway inflammation when administered at the time of allergen challenge.},
  author       = {Holgado Munoz, Aurora and Braun, Harald and Van Nuffel, Elien and Detry, Sammy and Schuijs, Martijn and Deswarte, Kim and Vergote, Karl and Haegman, Mira and Baudelet, Griet and Haustraete, Jurgen and Hammad, Hamida and Lambrecht, Bart and Savvides, Savvas and Afonina, Inna and Beyaert, Rudi},
  issn         = {0091-6749},
  journal      = {JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY},
  keywords     = {INNATE LYMPHOID-CELLS,TYPE-2 INFLAMMATION,SOLUBLE ST2,INTERLEUKIN 33,SEVERE ASTHMA,IDENTIFICATION,RECEPTOR,DISEASE,IMMUNOGENICITY,ASSOCIATION,IL-33,soluble ST2,antagonist,airway inflammation,allergic asthma},
  language     = {eng},
  number       = {1},
  pages        = {204--215},
  title        = {IL-33trap is a novel IL-33-neutralizing biologic that inhibits allergic airway inflammation},
  url          = {http://dx.doi.org/10.1016/j.jaci.2019.02.028},
  volume       = {144},
  year         = {2019},
}

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