AUTHOR=Frezza Valentina , Najda Zaneta , Davidovich Pavel , Sullivan Graeme P. , Martin Seamus J. TITLE=IL-1α and IL-36 Family Cytokines Can Undergo Processing and Activation by Diverse Allergen-Associated Proteases JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.879029 DOI=10.3389/fimmu.2022.879029 ISSN=1664-3224 ABSTRACT=
Inflammation driven by environmental allergens is an important source of morbidity in diseases such as asthma and eczema. How common allergens promote inflammation is still poorly understood, but previous studies have implicated the protease activity associated with many allergens as an important component of the pro-inflammatory properties of these agents. The IL-1 family cytokine, IL-33, has recently been shown to undergo processing and activation by proteases associated with multiple common allergens. However, it remains unclear whether the sensing of exogenous protease activity—as a proxy for the detection of invasive microbes, allergens and parasitic worms—is a general property of IL-1 family cytokines. In common with the majority of IL-1 family members, cytokines within the IL-36 sub-family (IL-36α, IL-36β and IL-36γ) are expressed as inactive precursors that require proteolysis within their N-termini for activation. Here we show that proteases associated with multiple common allergens of plant, insect, fungal and bacterial origin (including: