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

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.