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ALLERGIES

IL-33 meets allergens at the gate

Nature Immunology volume 19, pages 318–320 (2018)Cite this article

IL-33 is a mediator of allergic inflammation and is localized in mucosal tissues to respond rapidly to environmental insults. These include allergens themselves, which can directly activate IL-33 through their intrinsic proteolytic activity.

IL-33 is a cytokine that promotes allergic inflammation by activating a wide array of innate and adaptive immune cells. IL-33 normally resides within structural cells in the respiratory tract as an inactive nuclear protein. Unlike the release of classic cytokines, which are actively secreted, the release of IL-33 occurs in the context of stress or damage via incompletely defined processes. Proteolytic processing is needed to liberate its chromatin-binding domain from the cytokine domain in order to produce a more-potent cytokine; a key question has revolved around understanding where and how this processing occurs. Published work has shown that extracellular proteases from locally activated neutrophils or mast cells are one source of this activity1,2. In this issue of Nature Immunology, Cayrol et al. expand on their previous work and demonstrate that the proteolytic activity inherent in allergens themselves converts IL-33 into a fully active cytokine3. This finding sheds new light on the regulation of IL-33 and its potential contribution to allergic inflammation. Similar findings have also been reported in a published study that demonstrates IL-33 can be processed by the fungus Alternaria alternata or calpain-associated protease activity and provides evidence of processed forms of IL-33 in human samples4.

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Fig. 1: Release of IL-33 in the context of allergen exposure.

Katie Vicari/Nature Publishing Group

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  1. Insight BioConsulting, Bainbridge Island, WA, USA

    Dirk E. Smith

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  1. Dirk E. Smith
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Correspondence to Dirk E. Smith.

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Smith, D.E. IL-33 meets allergens at the gate. Nat Immunol 19, 318–320 (2018). https://doi.org/10.1038/s41590-018-0069-3

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