# IL‐33 Elicits LTC4 Synthesis in Allergic Inflammation via ST2‐Mediated Activation of Eosinophils

## TL;DR

This study shows that IL-33 activates eosinophils through the ST2 receptor to produce LTC4, a key mediator in allergic inflammation.

## Contribution

The study reveals a novel mechanism by which IL-33/ST2 signaling triggers LTC4 synthesis in eosinophils during allergic inflammation.

## Key findings

- ST2 activation is a key step in LTC4 synthesis by lipid body-enriched eosinophils in allergic inflammation.
- Exogenous IL-33 induces LTC4 production from activated eosinophils both in vivo and in vitro.
- The IL-33/ST2-driven LTC4 synthesis may offer therapeutic potential for cysteinyl leukotriene-mediated conditions.

## Abstract

Like pieces of a puzzle, IL‐33, eosinophils, and cysteinyl leukotrienes seem to come together and orchestrate allergic inflammation. While the IL‐33/ST2 receptor axis is known to activate some classical eosinophil functions, its ability to specifically trigger LTC4 synthesis remains elusive. Here, employing a murine model of allergic inflammation, ST2 activation emerged as a key step to LTC4 synthesis, primarily achieved by lipid bodies‐enriched eosinophils. Concurring, exogenous IL‐33 elicited LTC4 synthesis from activated eosinophils, both in vivo and from human cells in vitro. Thus, relevant to eosinophil‐regulated environments, such IL‐33/ST2‐driven cellular effect may bear therapeutic potential as a target in cysteinyl leukotrienes‐mediated conditions.

Allergic reaction‐derived IL‐33 activates ST2 to trigger selective eosinophil activation. IL‐33 in a type 2 immune response environment induces biogenesis of lipid bodies in eosinophils, platforms for the generation of lipid mediators, and selectively triggers LTC4 production.