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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

Antibodies targeting the shared cytokine receptor IL-1 receptor accessory protein invoke distinct mechanisms to block all cytokine signaling

Author

  • James K. Fields
  • Elin Jaensson Gyllenbäck
  • Marek Bogacz
  • Juliet Obi
  • Gabriel Svensson Birkedal
  • Kjell Sjöström
  • Kino Maravillas
  • Caitríona Grönberg
  • Sara Rattik
  • Kyle Kihn
  • Maria Flowers
  • Ally K. Smith
  • Nils Hansen
  • Thoas Fioretos
  • Chau Huyhn
  • David Liberg
  • Daniel Deredge
  • Eric J. Sundberg
Show all

Summary, in English

Interleukin-1 (IL-1)-family cytokines are potent modulators of inflammation, coordinating a vast array of immunological responses across innate and adaptive immune systems. Dysregulated IL-1-family cytokine signaling, however, is involved in a multitude of adverse health effects, such as chronic inflammatory conditions, autoimmune diseases, and cancer. Within the IL-1 family of cytokines, six—IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ—require the IL-1 receptor accessory protein (IL-1RAcP) as their shared co-receptor. Common features of cytokine signaling include redundancy of signaling pathways, sharing of cytokines and receptors, pleiotropy of the cytokines themselves, and multifaceted immune responses. Accordingly, targeting multiple cytokines simultaneously is an emerging therapeutic strategy and can provide advantages over targeting a single cytokine pathway. Here, we show that two monoclonal antibodies, CAN10 and 3G5, which target IL-1RAcP for broad blockade of all associated cytokines, do so through distinct mechanisms and provide therapeutic opportunities for the treatment of inflammatory diseases.

Department/s

  • Division of Clinical Genetics
  • Targeted therapies in leukemia
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • Translational Genomic and Functional Studies of Leukemia
  • LUCC: Lund University Cancer Centre
  • LTH Profile Area: Engineering Health

Publishing year

2024

Language

English

Publication/Series

Cell Reports

Volume

43

Issue

5

Document type

Journal article

Publisher

Cell Press

Topic

  • Immunology in the medical area

Keywords

  • 3G5
  • antibody
  • CAN10
  • CP: Immunology
  • cytokine
  • IL-1
  • IL-33
  • IL-36
  • shared receptor
  • signaling inhibition

Status

Published

Research group

  • Targeted therapies in leukemia
  • Translational Genomic and Functional Studies of Leukemia

ISBN/ISSN/Other

  • ISSN: 2211-1247