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Central domain of IL-33 is cleaved by mast cell proteases for potent activation of group-2 innate lymphoid cells

2014; National Academy of Sciences; Volume: 111; Issue: 43 Linguagem: Inglês

10.1073/pnas.1410700111

1091-6490

Emma Lefrançais, Anaïs Duval, Emilie Mirey, Stéphane Roga, Éric Espinosa, Corinne Cayrol, Jean‐Philippe Girard,

Eosinophilic Esophagitis

Significance Interleukin-33 (IL-33) is an IL-1 family cytokine with important roles in type-2 immunity and human asthma. IL-33 is a key activator of the recently described group-2 innate lymphoid cells (ILC2s), which are involved in the initiation of allergic inflammation. Here, we investigated the mechanisms regulating IL-33 activity. We discovered that mast cells, critical effector cells in allergic disorders, secrete proteases, which cleave IL-33 and generate mature forms with increased biological activity. We demonstrate that these mature forms of IL-33 are 30-fold more potent than full-length IL-33 for activation of ILC2s. Our study suggests that inhibition of IL-33 cleavage by mast cell and other inflammatory proteases could be useful to limit IL-33–mediated responses in allergic asthma and other inflammatory diseases.