# ST2+ Erythroid Progenitors Suppress Allergic Asthma by Scavenging IL‐33 in Young Mice

## TL;DR

ST2+ erythroid progenitors in young mice help prevent allergic asthma by removing IL-33 from the bloodstream.

## Contribution

Identifies a novel role for ST2+ erythroid progenitors in suppressing early-life allergic asthma via IL-33 scavenging.

## Key findings

- Plasma IL-33 levels peak at postnatal day 7 in mice.
- ST2+ erythroid progenitors efficiently scavenge IL-33 without significant signaling or gene changes.
- Depletion of ST2+ EPs worsens HDM-induced inflammation and increases Tfh and IgE+ B cells.

## Abstract

Although IL‐33/ST2 signaling has been implicated in adult asthma, its contribution to early‐onset allergic asthma remains poorly understood. Here, we examined the postnatal dynamics of IL‐33 and its regulation by splenic ST2+ erythroid progenitors (EPs).

Plasma IL‐33 levels were measured in neonatal and young mice. Wild Type (WT) and Il33
−/− mice were exposed to house dust mite (HDM) to assess airway inflammation and asthma. ST2+ EPs were analyzed for IL‐33 responsiveness, transcriptomic/epigenomic profiles, and IL‐33 scavenging capacity. EP depletion was performed to evaluate their role in HDM‐induced inflammation.

Plasma IL‐33 levels fluctuated during the postnatal period, peaking at postnatal day 7 (PND7). WT mice exhibited more severe HDM‐induced airway inflammation than Il33
−/− mice. Splenic ST2+ EPs, abundant in early life but absent by PND28, displayed minimal IL‐33–induced signaling or transcriptomic/epigenomic alterations, yet efficiently scavenged IL‐33. Depletion of EPs exacerbated HDM‐induced inflammation, accompanied by increased T follicular helper cells (Tfh) and IgE+ B cells.

ST2+ EPs function as transient IL‐33 scavengers during early life, attenuating its pro‐asthmatic effects and preserving immune homeostasis.