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Review Article

New perspectives on IL-33 and IL-1 family cytokines as innate environmental sensors

Ian C. Scott, D. Gareth Rees, E. Suzanne Cohen
Biochemical Society Transactions Oct 09, 2018, BST20170567; DOI: 10.1042/BST20170567
Ian C. Scott
Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Granta Park, Cambridge CB21 6GH, U.K.
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  • For correspondence: Scottia@medimmune.com
D. Gareth Rees
Department of Antibody Development and Protein Engineering, MedImmune, Granta Park, Cambridge CB21 6GH, U.K.
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E. Suzanne Cohen
Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Granta Park, Cambridge CB21 6GH, U.K.
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Abstract

Interleukin (IL)-1 family cytokines are important initiators of innate immunity and host defence; however, their uncontrolled activities can cause tissue-damaging inflammation. Consequently, IL-1 family cytokines have sophisticated regulatory mechanisms to control their activities including proteolytic processing for their activation and the deployment of soluble receptors and receptor antagonists to limit their activities. IL-33 is a promoter of type 2 immunity and allergic inflammation through its alarmin activity that can rapidly initiate local immune responses by stimulating innate immune cells following exposure to environmental insults, pathogens, or sterile injury. Recent publications have provided new insights into how the range and duration of IL-33 activity is regulated by direct sensing of host-derived and exogenous proteolytic activities as well as oxidative changes during tissue damage. Here, we discuss how this impacts our understanding of the roles of IL-33 in initiating immune responses and the evidence that these sensing mechanisms might regulate the activities of other IL-1 family cytokines and their biological functions. Finally, we discuss translational challenges these discoveries pose for the accurate detection of different forms of these cytokines.

  • alarmin
  • allergen
  • allergic
  • cytokines
  • immune response
  • interleukin
  • Abbreviations

    ALT,
    Alternaria alternata;
    DSB,
    disulfide bridges;
    DTT,
    dithiothreitol;
    FGF,
    fibroblast growth factor;
    FL,
    full length;
    IL,
    interleukin;
    PAR-2,
    proteinase-activated receptor-2
    • © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
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    New perspectives on IL-33 and IL-1 family cytokines as innate environmental sensors
    Ian C. Scott, D. Gareth Rees, E. Suzanne Cohen
    Biochemical Society Transactions Oct 2018, BST20170567; DOI: 10.1042/BST20170567
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    New perspectives on IL-33 and IL-1 family cytokines as innate environmental sensors
    Ian C. Scott, D. Gareth Rees, E. Suzanne Cohen
    Biochemical Society Transactions Oct 2018, BST20170567; DOI: 10.1042/BST20170567

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    • Article
      • Abstract
      • IL-33 and IL-1 family cytokines regulate immune responses and inflammation
      • IL-33 and IL-1 family cytokines sense the proteolytic microenvironment
      • IL-33 and IL-1 family cytokines can sense the oxidative microenvironment
      • Potential implications for measurement of IL-33 and IL-1 family cytokines
      • Competing Interests
      • Acknowledgements
      • References
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    Keywords

    alarmin
    allergen
    allergic
    cytokines
    immune response
    interleukin

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