Ripping the Ripoptosome: a novel path for blocking allergic inflammation?

Jutta Horejs-Hoeck,Theresa Neuper,Richard Weiss

doi:10.1038/s41423-021-00815-4

Abstract

Ripping the Ripoptosome: a novel path for blocking allergic inflammation?

Highlights

By employing a pan-caspase inhibitor to block intracellular caspase activity, Brusilovsky et al showed that allergen-induced caspase 8 activation is required for the cleavage of downstream caspases 3 and 7, which results in the intracellular processing of IL-33
Experiments using epithelial cells overexpressing the intracellular IL-33 precursor revealed that caspase 3 and caspase 7, but not caspase 8, cleave premature IL-33 into the biologically active mature IL-33 protein
This finding suggests that allergen-induced release of IL-33 by epithelial cells requires RIPK-1 phosphorylation and subsequent degradation of phosphorylated RIPK-1, activation of caspase 8, and cleavage of downstream caspases 3 and 7

Summary

Introduction

Allergies are an unremitting global health care problem. the symptoms of affected individuals are well documented for a wide range of allergic disorders, the precise molecular mechanisms that trigger allergic inflammation to innocuous substances remain elusive. The authors showed that allergens derived from a wide range of organisms, including fungi, cockroaches and mites, but not pollen or food allergens, induce intracellular maturation and subsequent secretion of IL-33 by epithelial cells. By employing a pan-caspase inhibitor to block intracellular caspase activity, Brusilovsky et al showed that allergen-induced caspase 8 activation is required for the cleavage of downstream caspases 3 and 7, which results in the intracellular processing of IL-33.

Results

Conclusion