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Interleukin 33 is a guardian of barriers and a local alarmin

Nature Immunology volume 17, pages 122–131 (2016)Cite this article

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Abstract

Interleukin 33 (IL-33) is a member of the IL-1 family of cytokines with a growing number of target cells and a plethora of biological functions. Although it has commonalities with other IL-1 cytokines, IL-33 exhibits some unique features. Here we review the biology of IL-33 and its receptor and develop a working model that describes two 'lives' for IL-33—one intracellular and one extracellular. Under healthy conditions, constitutively produced, intracellular IL-33 participates in maintaining barrier function by regulating gene expression as a nuclear protein. In parallel, nuclear IL-33 functions as a stored alarmin that is released when barriers are breached. Extracellular IL-33 coordinates immune defense and repair mechanisms while also initiating differentiation of helper T cells as the adaptive immune response is triggered.

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Figure 1: Production, release and processing of IL-33.
Figure 2: Formation and fate of IL-33R complexes.
Figure 3: Working model of IL-33 as a guardian of barriers and conductor of local inflammation.

Marina Corral Spence/Nature Publishing Group

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  1. Institute of Cellular Chemistry, Center for Biochemistry, Hannover Medical School, Hannover, Germany

    Nikolas T Martin

  2. Immunology FB08, Justus-Liebig-University Giessen, Giessen, Germany

    Michael U Martin

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Martin, N., Martin, M. Interleukin 33 is a guardian of barriers and a local alarmin. Nat Immunol 17, 122–131 (2016). https://doi.org/10.1038/ni.3370

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