Mucosal Immunol. 2026 Jan 7:S1933-0219(26)00002-4. doi: 10.1016/j.mucimm.2026.01.002. Online ahead of print.
ABSTRACT
Type 2 cytokinerelease promotes wound healing and helminth clearance, but it remains unclearwhethergroup 2 innate lymphocytes (ILC2s) and T-helper2 cells (TH2) cells have functionally distinctroles during anamnestic immunity. This study demonstrates that ILC2 can prevent re-infection andlimit tissue injury caused by the helminthNippostrongylus brasiliensis (Nb). TH2 cells were necessary during initial antigen encounter but dispensable forearly pathogen clearance and lungrepairafterILC2 priming. Upon re-infection, trained ILC2 selectively blocked interleukin (IL)-17+ γδT cell expansion and infection-induced lung injury through an Amphiregulin (Areg)-independent mechanism. Trained ILC2s had a distinct metabolic gene expression profile marked by elevated tryptophan hydroxylase 1(Tph1) and pulmonary serotonin levels were largely ILC2-dependent. Surprisingly, serotonin prevented IL-17-associated lung hemorrhage irrespective of parasite load. We propose that TH2-ILC2 interactions drive pathogen control, but ILC2 distinctly control lung tissuerepairthrough serotonin.
PMID:41513004 | DOI:10.1016/j.mucimm.2026.01.002