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

Fields, James K. ; Gyllenbäck, Elin Jaensson LU ; Bogacz, Marek ; Obi, Juliet ; Birkedal, Gabriel Svensson LU ; Sjöström, Kjell ; Maravillas, Kino ; Grönberg, Caitríona LU ; Rattik, Sara LU and Kihn, Kyle , et al. (2024) In Cell Reports 43(5).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
3G5, antibody, CAN10, CP: Immunology, cytokine, IL-1, IL-33, IL-36, shared receptor, signaling inhibition
in
Cell Reports
volume
43
issue
5
article number
114099
publisher
Cell Press
external identifiers
  • pmid:38636519
  • scopus:85191854674
ISSN
2211-1247
DOI
10.1016/j.celrep.2024.114099
language
English
LU publication?
yes
id
85a3f796-a433-4fb0-9997-6141cc253402
date added to LUP
2024-05-15 12:08:26
date last changed
2024-11-14 07:50:43
@article{85a3f796-a433-4fb0-9997-6141cc253402,
  abstract     = {{<p>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.</p>}},
  author       = {{Fields, James K. and Gyllenbäck, Elin Jaensson and Bogacz, Marek and Obi, Juliet and Birkedal, Gabriel Svensson and Sjöström, Kjell and Maravillas, Kino and Grönberg, Caitríona and Rattik, Sara and Kihn, Kyle and Flowers, Maria and Smith, Ally K. and Hansen, Nils and Fioretos, Thoas and Huyhn, Chau and Liberg, David and Deredge, Daniel and Sundberg, Eric J.}},
  issn         = {{2211-1247}},
  keywords     = {{3G5; antibody; CAN10; CP: Immunology; cytokine; IL-1; IL-33; IL-36; shared receptor; signaling inhibition}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Antibodies targeting the shared cytokine receptor IL-1 receptor accessory protein invoke distinct mechanisms to block all cytokine signaling}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2024.114099}},
  doi          = {{10.1016/j.celrep.2024.114099}},
  volume       = {{43}},
  year         = {{2024}},
}