Interleukin-25: orchestrating resistance to intestinal helminth infections.

Interleukin-25 (IL-25) has emerged as a central regulator of type 2 immunity at mucosal surfaces. Beyond its classical role as an epithelial alarmin, IL-25 acts as a multifunctional coordinator of epithelial sensing, immune activation, and tissue adaptation during helminth infection. In the intestine, tuft cells detect helminth- and microbiota-derived metabolites and activate a feed-forward circuit with type 2 innate lymphoid cells (ILC2s), promoting antiparasitic immunity and barrier protection. Emerging evidence further links IL-25 to neuroimmune communication, epithelial remodeling, tissue resilience, and disease tolerance. Here, we summarize recent advances in IL-25 biology, including ILC2 specialization and the distinct roles of IL-25 in nematode and trematode infections, highlighting its potential as a therapeutic target to enhance mucosal protection while limiting immunopathology.