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IL-1R3 blockade broadly attenuates the functions of six members of the IL-1 family, revealing their contribution to models of disease

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Jesper Falkesgaard Højen
  • Marie Louise Vindvad Kristensen, University of Colorado Denver
  • ,
  • Amy S. McKee, University of Colorado Denver
  • ,
  • Megan Taylor Wade, University of Colorado Denver
  • ,
  • Tania Azam, University of Colorado Denver
  • ,
  • Lars P. Lunding, Research Centre Borstel
  • ,
  • Dennis M. de Graaf, University of Colorado Denver, Radboud University Nijmegen
  • ,
  • Benjamin J. Swartzwelter, University of Colorado Denver
  • ,
  • Michael Wegmann, Research Centre Borstel
  • ,
  • Martin Tolstrup
  • Karsten Beckman, MAB Discovery GmbH
  • ,
  • Mayumi Fujita, University of Colorado Denver
  • ,
  • Stephan Fischer, MAB Discovery GmbH
  • ,
  • Charles A. Dinarello, University of Colorado Denver, Radboud University Nijmegen

Interleukin (IL)-1R3 is the co-receptor in three signaling pathways that involve six cytokines of the IL-1 family (IL-1α, IL-1β, IL-33, IL-36α, IL-36β and IL-36γ). In many diseases, multiple cytokines contribute to disease pathogenesis. For example, in asthma, both IL-33 and IL-1 are of major importance, as are IL-36 and IL-1 in psoriasis. We developed a blocking monoclonal antibody (mAb) to human IL-1R3 (MAB-hR3) and demonstrate here that this antibody specifically inhibits signaling via IL-1, IL-33 and IL-36 in vitro. Also, in three distinct in vivo models of disease (crystal-induced peritonitis, allergic airway inflammation and psoriasis), we found that targeting IL-1R3 with a single mAb to mouse IL-1R3 (MAB-mR3) significantly attenuated heterogeneous cytokine-driven inflammation and disease severity. We conclude that in diseases driven by multiple cytokines, a single antagonistic agent such as a mAb to IL-1R3 is a therapeutic option with considerable translational benefit.

TidsskriftNature Immunology
Sider (fra-til)1138-1149
Antal sider12
StatusUdgivet - 2019

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