Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation

• DOI: 10.1038/ncomms9327
• Publication Date: 2015-09-14T09:51:45Z
• Authors: E. Suzanne Cohen; Ian C. Scott; Jayesh B. Majithiya; Laura Rapley; Benjamin P. Kemp; Elizabeth England; D. Gareth Rees; Catherine L. Over...; Joanne Woods; Nicholas J. Bond; Christel Séguy Ve...; Kevin J. Embrey; Dorothy A. Sims; Michael R. Snaith; Katherine A. Vousden; Martin D. Strain; Denice T. Y. Chan; Sara Carmen; Catherine E. Hunt...; Liz Flavell; Jianqing Xu; Bojana Popovic; Christopher E. Br...; Tristan J. Vaughan; Robin Butler; David C. Lowe; Daniel R. Higazi; Dominic J. Corkill; Richard D. May; Matthew A. Sleeman; Tomas Mustelin
• Keywords: Interleukin 33

Abstract In response to infections and irritants, the respiratory epithelium releases alarmin interleukin (IL)-33 elicit a rapid immune response. However, little is known about regulation of IL-33 following its release. Here we report that biological activity at receptor ST2 rapidly terminated in extracellular environment by formation two disulphide bridges, resulting an extensive conformational change disrupts binding site. Both reduced (active) bonded (inactive) forms can be detected lung lavage samples from mice challenged with Alternaria extract sputum patients moderate–severe asthma. We propose this mechanism for inactivation secreted constitutes ‘molecular clock’ limits range duration ST2-dependent immunological responses airway stimuli. Other IL-1 family members are also susceptible cysteine oxidation changes could regulate their systemic exposure through similar mechanism.